tag:theconversation.com,2011:/africa/topics/stem-cell-2838/articlesStem cell – The Conversation2023-01-11T13:25:40Ztag:theconversation.com,2011:article/1915592023-01-11T13:25:40Z2023-01-11T13:25:40ZTriggering cancer cells to become normal cells – how stem cell therapies can provide new ways to stop tumors from spreading or growing back<figure><img src="https://images.theconversation.com/files/503356/original/file-20230105-19-bvp86r.jpg?ixlib=rb-1.1.0&rect=6%2C6%2C2038%2C2038&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">This image shows pancreatic cancer cells (blue) growing, encased within membranes (red).</span> <span class="attribution"><a class="source" href="https://flic.kr/p/GAACEb">Min Yu/Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC via NIH/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>How cells <a href="https://doi.org/10.3390%2Fijms21186489">become cancerous</a> is a process researchers are still trying to fully understand. Generally, normal cells grow and multiply through controlled cell division, where <a href="https://doi.org/10.3389/fcell.2021.645593">old and damaged cells</a> are replaced after they die by new cells. Sometimes this process stops working, leading cells to start growing uncontrollably and develop into a tumor.</p>
<p>Traditionally, cancer treatments like chemotherapy, immunotherapy, radiation and surgery focus on killing cancer cells. Another type of treatment using stem cells called <a href="https://doi.org/10.1177/1010428317729933">differentiation therapy</a>, however, focuses on persuading cancer cells to become normal cells. </p>
<p><a href="https://scholar.google.com/citations?user=GNSivG8AAAAJ&hl=en">We are</a> <a href="https://chen.uchicago.edu/abhimanyu-thakur-ph-d/">researchers</a> who study how stem cells, or immature cells that can develop into different types of cells, behave in states of health and disease. We believe that stem cells can provide potential treatments for cancer of all types in many different ways.</p>
<h2>How do stem cells contribute to cancer?</h2>
<p><a href="https://www.the-scientist.com/university/brush-up-what-is-stemness-and-pluripotency-70571">Stem cells</a> are unspecialized cells, meaning they can eventually become any one of the various types of cells that make up different parts of the body. They can replenish cells in the skin, bone, blood and other organs during development, and regenerate and repair tissues when they’re damaged.</p>
<p>There are different types of stem cells. Embryonic stem cells are the first cells that initially form after a sperm fertilizes an egg, and can give rise to all other cell types in the human body. Adult stem cells are more mature, meaning they can replace damaged cells only in one type of organ and have a limited ability to multiply. Researchers can <a href="https://doi.org/10.1007%2Fs13238-021-00863-6">reprogram adult stem cells, or differentiated cells</a>, in the lab to act like embryonic stem cells.</p>
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<figcaption><span class="caption">Cells become specialized over the course of development.</span></figcaption>
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<p>Because stem cells can survive longer than regular cells, they have a much higher probability of accumulating genetic mutations that can result in loss of control over their growth and ability to regenerate. This is why many tumors harbor a small subpopulation of cells that <a href="https://doi.org/10.1038%2Flabinvest.2008.14">function like stem cells</a>. These so-called cancer stem cells are <a href="https://doi.org/10.1186/s13578-017-0188-9">thought to be responsible</a> at least in part for cancer initiation, progression, metastasis, recurrence and treatment resistance.</p>
<h2>What is differentiation therapy?</h2>
<p>Accumulating evidence is also showing that cancer stem cells can differentiate into multiple cell types, including noncancerous cells. Researchers are taking advantage of this fact through a type of treatment called <a href="https://doi.org/10.1177/1010428317729933">differentiation therapy</a>. </p>
<p>The concept of differentiation therapy <a href="https://doi.org/10.1038/nrc.2017.103">originated from scientists observing</a> that hormones and cytokines, which are proteins that play a key role in cell communication, can stimulate stem cells to mature and lose their ability to regenerate. It followed that forcing cancer stem cells to differentiate into more mature cells could subsequently stop them from multiplying uncontrollably, making them become normal cells.</p>
<p>Differentiation therapy has been successful in treating <a href="https://doi.org/10.1182/blood-2009-01-198911">acute promyelocytic leukemia</a>, an aggressive blood cancer. In this case, retinoic acid and arsenic are used to block a protein that stops myeloid cells, a type of blood cell derived from the bone marrow, from fully maturing. By allowing these cells to fully mature, they lose their cancerous qualities.</p>
<p>Furthermore, because differentiation therapy doesn’t focus on killing cancer cells and doesn’t surround healthy cells in the body with harmful chemicals, it can be <a href="https://doi.org/10.1182%2Fblood-2009-01-198911">less toxic</a> than traditional treatments.</p>
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<a href="https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of acute promyelocytic leukemia" src="https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Acute promyelocytic leukemia, as shown in this microscopy image, can be treated with differentiation therapy.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/acute-promyelocytic-leukemia-cells-royalty-free-image/1417347912">jarun011/iStock via Getty Images Plus</a></span>
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<h2>Using stem cells to treat cancer</h2>
<p>There are many other potential ways to use stem cells to treat cancer. For example, cancer stem cells can be <a href="https://doi.org/10.1038/s41392-020-0110-5">directly targeted</a> to stop their growth, or turned into “<a href="https://doi.org/10.1515/iss-2016-0005">Trojan horses</a>” that attack other tumor cells.</p>
<p><a href="https://doi.org/10.1155/2016/1740936">Quiescent cancer stem cells</a>, which don’t divide but are still alive, are another potential drug target. These cells typically play a big role in treatment resistance for various cancer types because they are able to regenerate and avoid death even better than regular cancer stem cells. Their quiescent quality can persist for decades and lead to a cancer relapse. They are also challenging to distinguish from regular cancer stem cells, making them difficult to study.</p>
<p>Researchers can also genetically engineer stem cells to express a protein that binds to a desired target in a cancer cell, increasing the efficacy of treatments by releasing drugs right at the tumor. For example, <a href="https://doi.org/10.3389%2Ffbioe.2020.00043">mesenchymal stem cells</a> derived from bone marrow naturally migrate toward and stick to tumors, and can be used to deliver cancer drugs directly to cancer cells.</p>
<p>Stem cells can also be used to make <a href="https://doi.org/10.1002/wdev.399">organoid models</a>, or miniature versions of organs, to screen potential cancer drugs and study the underlying mechanisms that lead to cancer. </p>
<h2>Challenges in stem cell therapy</h2>
<p>Although, stem cells hold numerous advantages in their use in cancer therapy, they also <a href="https://doi.org/10.18632%2Foncotarget.20798">face various challenges</a>. For example, many current stem cell therapies that aren’t used in combination with other drugs are unable to completely eliminate tumors. There are also concerns about stem cell therapies potentially promoting tumor growth.</p>
<p>Despite these challenges, we believe that stem cell technologies have the potential to open new avenues for cancer therapy. Integrating genetic engineering with stem cells can overcome the major drawbacks of chemotherapeutics, such as toxicity to healthy cells. With further research, cancer stem cell therapies may one day become part of the standard of care for many types of cancer.</p><img src="https://counter.theconversation.com/content/191559/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Many tumors have cancer stem cells that help them grow and evade treatments. Differentiation therapy forces these cells to mature, stopping growth with less toxicity than traditional treatments.Huanhuan Joyce Chen, Assistant Professor of Molecular Engineering, University of Chicago Pritzker School of Molecular EngineeringAbhimanyu Thakur, Postdoctoral Scholar in Molecular Engineering, University of Chicago Pritzker School of Molecular EngineeringLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1106422019-02-05T11:40:31Z2019-02-05T11:40:31ZStem cell treatments for arthritic knees are unproven, expensive and potentially dangerous<figure><img src="https://images.theconversation.com/files/256445/original/file-20190130-108334-eplgb0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">An X-ray of both knees reveals a narrow space between joints caused by loss of cartilage. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/osteoarthritis-knee-oa-film-xray-both-320994311?src=Kou3_n7urkrDTi76OUcB0g-1-94">Puwadol Jaturawutthichai/Shutterstock.com</a></span></figcaption></figure><p>Twelve patients who tried injections of stem cells were hospitalized with infections, according to <a href="https://www.nytimes.com/2018/12/20/health/stem-cell-shots-bacteria-fda.html">a report in The New York Times</a> that should cause patients concern. More important is that they should investigate stem cell treatments, for conditions such as cartilage injuries to their joints, before committing to one of these procedures. It’s also a valuable reminder that physicians need to work closely with patients to help them understand their options and which choice may be best for them.</p>
<p>Stem cells are “uncommitted” cells that are, at least theoretically, capable of <a href="https://stemcells.nih.gov/info/basics/1.htm">becoming any type of cell</a> – skin, heart, kidney or even knee cartilage cells. Stem cells can come from fetal tissue, including products of in-vitro fertilization as well as placenta and umbilical cord tissue. They can also come from a patient’s own “hidden” adult stem cells, which are most often harvested from bone marrow and fat. The potential for using these cells in medicine is tremendous; for instance, stem cell transplants are used <a href="https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/stem-cell-transplant/types-of-transplants.html">frequently to treat certain cancers</a>, such as leukemias and blood disorders.</p>
<p>I am a professor of orthopedic surgery at the University of Virginia. I am also a victim of knee <a href="https://www.niams.nih.gov/health-topics/osteoarthritis">osteoarthritis</a> and have gone through knee replacements for both of my knees a little over a year ago. Since then I have made it my mission to educate the public about this condition, and to try to keep the enthusiasm regarding new cutting-edge options in check. That is because I have seen many patients who have paid thousands of dollars for a so-called stem cell treatment only to discover later that they were duped. In most cases fortunately, the only injury was to their wallet.</p>
<p>According to the Arthritis Foundation, <a href="https://www.arthritis.org/about-arthritis/understanding-arthritis/arthritis-statistics-facts.php">at least 31 million Americans</a> are affected with osteoarthritis, the most common type of cartilage wear. A quick web search will confirm just how popular “stem cell treatment” is, and how industry and many institutions offer this option.</p>
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<img alt="" src="https://images.theconversation.com/files/256439/original/file-20190130-108338-1eih5kg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/256439/original/file-20190130-108338-1eih5kg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=419&fit=crop&dpr=1 600w, https://images.theconversation.com/files/256439/original/file-20190130-108338-1eih5kg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=419&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/256439/original/file-20190130-108338-1eih5kg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=419&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/256439/original/file-20190130-108338-1eih5kg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=526&fit=crop&dpr=1 754w, https://images.theconversation.com/files/256439/original/file-20190130-108338-1eih5kg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=526&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/256439/original/file-20190130-108338-1eih5kg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=526&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">The four stages of knee osteoarthritis.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/stages-knee-osteoarthritis-oa-224218837?src=Kou3_n7urkrDTi76OUcB0g-1-40">Designua/Shutterstock.com</a></span>
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<h1>The truth about stem cells</h1>
<p>Unfortunately, the excitement about <a href="https://doi.org/10.1007/5584_2018_205">stem cells</a> <a href="https://www.webmd.com/osteoarthritis/news/20170407/stem-cells-for-knees-promising-treatment-or-hoax#1">has outpaced the science</a> in <a href="http://doi.org/10.1007/5584_2018_205">many areas of health care</a>. In addition, due to <a href="http://doi.org/10.1210/er.2008-0031">ethical issues</a> associated with the use of fetal tissue, the U.S. Food and Drug Administration <a href="https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm286155.htm">has severely restricted its use</a>. Adult stem cells have fewer regulatory issues, but the <a href="https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm286155.htm">FDA has prohibited “manipulation,”</a> which includes processing and culturing of these cells. Therefore, obtaining an abundant source of concentrated stem cells can be difficult. </p>
<p><a href="http://doi.org/10.4252/wjsc.v6.i5.629">In orthopedics, researchers have proposed using stem cells</a> for the treatment of joint – cartilage damage. This includes <a href="https://www.niams.nih.gov/health-topics/osteoarthritis">osteoarthritis</a>, the thinning of cartilage that causes bones to rub against one another – similar to a car tire going bald after 50,000 miles. Osteoarthritis is the primary cause of <a href="https://www.niams.nih.gov/health-topics/joint-replacement-surgery">joint replacement surgery</a>, and stem cell injections have been promoted as a potential way to avoid joint replacement by regenerating cartilage. Unfortunately, current technology and regulatory issues make obtaining and concentrating true stem cells a challenge, and encouraging them to become and remain cartilage cells and nothing else is even more difficult. </p>
<p>The problem with stem cells is that these cells can continue to evolve; they may not stop development at the cartilage cell phase. They may continue to differentiate into bone cells. This would make the joint even worse because bone creates a rough surface adjacent to the smooth articular cartilage. Bone is actually the end result of arthritis.</p>
<p>According to the American Association of Hip and Knee Surgeons, there are <a href="https://hipknee.aahks.org/can-stem-cell-therapy-help-my-joint-pain/">no proven uses of pain medications or therapies</a> that can delay or reverse the progressive joint destruction that occurs with osteoarthritis. </p>
<p>Any positive effects of current stem cell treatment are likely not the result of the actual cells themselves but something else.</p>
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<a href="https://images.theconversation.com/files/257077/original/file-20190204-193213-gfk67q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/257077/original/file-20190204-193213-gfk67q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/257077/original/file-20190204-193213-gfk67q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=456&fit=crop&dpr=1 600w, https://images.theconversation.com/files/257077/original/file-20190204-193213-gfk67q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=456&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/257077/original/file-20190204-193213-gfk67q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=456&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/257077/original/file-20190204-193213-gfk67q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=573&fit=crop&dpr=1 754w, https://images.theconversation.com/files/257077/original/file-20190204-193213-gfk67q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=573&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/257077/original/file-20190204-193213-gfk67q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=573&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">This is an example of a total knee replacement.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/total-knee-replacement-surgery-94626556?src=ArVhW9WT7ctYHTgLs6aoOw-1-29">Alila Medical Media/SHutterstock.com</a></span>
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<h2>Alternatives to stem cells</h2>
<p>Separating the hype from the reality about the use of stem cells for cartilage injuries is a reminder that all patients – with advice from their doctors – need a clear picture of the potential benefits and side effects of their treatment options. This includes complications from harvesting bone marrow from the pelvis - which actually only contain less than 0.01 percent stem cells - including fracture and injury to adjacent structures and infection as detailed in The New York Times article. And while harvesting fat may seem even more attractive, the yield of actual stem cells may be even less.</p>
<p>Depending on the cause and severity of their knee pain, for example, patients have treatment options that range from physical therapy to injections of various medications to surgery. All have pros and cons; steroid injections can provide quick but short-lived pain relief, while a knee replacement can provide a permanent solution but also requires months of rehabilitation. Doctors need to help patients make the choice that best fits their particular needs.</p>
<p>So while a quick internet search may find clinics that offer stem cell treatments for cartilage injuries that cost thousands of dollars - and are almost always not covered by insurance - I strongly recommend that consumers remember the concept of “buyer beware” and that medical providers remember the Hippocratic principle: “first do no harm.”</p><img src="https://counter.theconversation.com/content/110642/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Miller is a consultant for Arthrex, a maker of medical implants and receives royalties from Elsevier and Wolters-Kluwer medical publishing companies. </span></em></p>When it comes to seeking out stem cell treatments for joint injuries, buyer beware. These so-called miracle treatments are often scams, so it vital for patients to discuss options with a physician.Mark Miller, Professor of Orthopaedic Surgery, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1109212019-02-04T12:30:28Z2019-02-04T12:30:28ZCancer growth in the body could originate from a single cell – target it to revolutionise treatment<figure><img src="https://images.theconversation.com/files/257009/original/file-20190204-193213-1tzdd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/cancer-cells-3d-illustration-574815085?src=Bz5qM75AljUdBvqrlw6Bfg-1-3">Andrii Vodolazhskyi/Shutterstock</a></span></figcaption></figure><p>Cancer remains a frightening and largely incurable disease. The toxic side effects of chemotherapy and radiation make the cure often seem as bad as the ailment, and there is also the threat of recurrence and tumour spread.</p>
<p>Cancer treatment still follows a practically medieval method of cut, burn or poison. If the growth can’t be cut out through surgery, it may be burnt away with radiation or poisoned by chemotherapy. As a result, cancer therapy remains a daunting diagnosis for patients and treatment options seem limited for a disease which causes <a href="https://www.who.int/news-room/fact-sheets/detail/cancer">one in six deaths globally</a>.</p>
<p>The failure to innovate in cancer treatment may lie in the very poor success rate of clinical trials. Approximately 95%-98% of new anti-cancer drugs <a href="https://academic.oup.com/biostatistics/advance-article/doi/10.1093/biostatistics/kxx069/4817524">actually fail phase III clinical trials</a>, the phase in which <a href="https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/what-clinical-trials-are/phases-of-clinical-trials#phase3">new treatments are compared</a> with existing therapy options. This is a staggering statistic. No other business could possibly survive with such an abysmal success rate.</p>
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<span class="caption">Chemotherapy and radiotherapy are broad-based treatments which attack the bulk of cancer cells but also damage healthy tissue.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/cancer-patients-receiving-chemotherapy-treatment-hospital-529109200?src=PhgS1fo7VEItjr0JsbMkcQ-1-0">Napocska/Shutterstock</a></span>
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<p>Most drugs are made to target “bulk” cancer cells, but not the root cause: the cancer stem cell. Cancer stem cells, also known as “tumour-initiating cells”, are the only cells in the tumour <a href="https://www.nature.com/articles/nature09781">that can make a new tumour</a>. New therapies that specifically target and eradicate these cancer stem cells are needed to prevent tumours growing and spreading, but for that there needs to be more clarity around the target.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941316/">Our new research</a> may have discovered such a target. We have identified and isolated cells within different cancerous growths which we call the “cell of origin”. Our experiments on cancer cells derived from a human breast tumour found that stem cells – representing 0.2% of the cancer cell population – have special characteristics.</p>
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Read more:
<a href="https://theconversation.com/drug-resistant-cancers-kill-millions-heres-how-were-tackling-them-78208">Drug-resistant cancers kill millions – here's how we're tackling them</a>
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<p>They generate <a href="https://www.frontiersin.org/articles/10.3389/fonc.2018.00677/abstract">vast amounts of energy and proliferate rapidly</a>. We believe that they resemble the cancer cell of origin that has escaped senescence – the natural process of cell ageing and “death” which concludes a healthy cell life cycle. These are thought to be the first cancer cells which start the process of uncontrolled cell multiplication and cause tumours to form.</p>
<p>These cancer stem cells undergo anchorage-independent growth, also known as growth in suspension, without any tissue attachment. This is how metastasis occurs – spreading via the blood vessels and lymphatic vessels. These features put them front and centre as a new target for anti-cancer therapy.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/257018/original/file-20190204-193195-10koi98.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/257018/original/file-20190204-193195-10koi98.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/257018/original/file-20190204-193195-10koi98.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/257018/original/file-20190204-193195-10koi98.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/257018/original/file-20190204-193195-10koi98.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/257018/original/file-20190204-193195-10koi98.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/257018/original/file-20190204-193195-10koi98.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Cancer stem cells grow in suspension in the bloodstream and spread throughout the body.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-rendering-red-blood-cells-vein-517874557?src=BvKWjBwOSlhDO4joRgHq1g-1-5">Phonlamai Photo/Shutterstock</a></span>
</figcaption>
</figure>
<p>With astonishing luck, these energetic cancer stem cells are colour-coded which means they have a natural phosphorescent glow, making them easy to identify and target.</p>
<p>Now that we have found them and we know how they behave, it should be relatively simple to find drugs to target cancer stem cells. <a href="https://www.frontiersin.org/articles/10.3389/fonc.2018.00677/abstract">In our new paper</a> we have already shown that they are easily targeted with a mitochondrial inhibitor or a cell cycle inhibitor <a href="https://www.breastcancercare.org.uk/information-support/facing-breast-cancer/going-through-breast-cancer-treatment/targeted-therapy/ribociclib-kisqali">such as Ribociclib</a>, an FDA-approved drug in the US which would prevent their proliferation. </p>
<p>Ultimately, this means that if we focus on energetic cancer stem cells, we may be able to directly hit the target. We might be able to turn cancer into a manageable chronic disease, like diabetes. We believe that we have arrived at the start of a new, more fruitful, road in cancer therapy. As a consequence, “big pharma” drug screening should actually focus on cancer stem cells and their relevant targets.</p><img src="https://counter.theconversation.com/content/110921/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael P. Lisanti holds a minority interest in Lunella Biotech, Inc.
</span></em></p>Cancer treatment could be revolutionised by the discovery of the origin cells which divide first.Michael P. Lisanti, Professor of Translational Medicine, University of SalfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/724932017-02-07T02:08:36Z2017-02-07T02:08:36ZYes there’s hope, but treating spinal injuries with stem cells is not a reality yet<figure><img src="https://images.theconversation.com/files/155776/original/image-20170206-27176-1fksxua.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Scientists hope that stem cells may be able to repair nerves and other cells that support transmission of electrical impulses in the spinal cord. </span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/binomialphoto/14498062329/in/photolist-o69mPT-nPzcgB-q2ScCx-HabFjj-nx69Av-okB9cC-pdnUNF-8fa2iw-onBsBN-o69WK8-Dw1FJr-52QWhj-gsCU4-29e3Ja-o6aPKn-sqwpb-6CatjE-48zVLm-onBL91-4XJsbd-aXVcLz-7UL65F-o69rTv-FPUved-bKcNCD-cnviq5-bJaZHF-bJb1f4-bJb47P-bJb3s8-bJbcXB-o69VBA-onrfrC-onqQYf-o6auvv-o6aSKR-o69JGQ-FRfE1-6ii6d2-onBotN-59uFJP-o6aCtp-o69wdy-ae72m-bRiR4Z-o6asyz-o69o6b-o69tQs-bJb3MP-bvgezU">binomialphoto/flickr </a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span></figcaption></figure><p>The <a href="http://www.australianoftheyear.org.au/honour-roll/?view=landing&year=2017">2017 Australian of the Year</a> award went to Professor Alan Mackay-Sim for his significant career in stem cell science. </p>
<p>The prize was linked to barbeque-stopping headlines equating his achievements to the scientific equivalent of “<a href="http://www.smh.com.au/federal-politics/political-news/alan-mackaysim-the-scientist-whose-miracle-made-a-paraplegic-walk-again-named-australian-of-the-year-20170125-gtyiq7.html">the moon landing</a>” and “<a href="http://www.3aw.com.au/news/alan-mackaysim-named-australian-of-the-year-20170125-gtyt48.html">paving the road to recovery</a>” for people with spinal cord injuries. </p>
<p>Such claims in the media imply that there is now a scientifically proven stem cell treatment for spinal cord injury. This is not the case. </p>
<p>For now, any clinic or headline claiming miracle cures should be viewed with caution, as they are likely to be trading on <a href="https://theconversation.com/the-future-of-stem-cells-tackling-hype-versus-hope-72052">people’s hope</a>.</p>
<h2>Why stem cells for spinal cord injury?</h2>
<p>Put simply, injury to the spinal cord causes damage to the nerve cells that transmit information between the brain and the rest of the body. </p>
<p>Depending on which part of the spine is involved, the injury can affect the nerves that control the muscles in our legs and arms; those that control bowel and bladder function and how we regulate body temperature and blood pressure; and those that carry the sensation of being touched. This occurs in part because injury and subsequent scarring affect not just the nerves but also the insulation that surrounds and protects them. The insulation – the myelin sheath – is damaged and the body cannot usually completely replace or regenerate this covering.</p>
<p>Stem cells can self-reproduce and grow into hundreds of different cell types, including nerves and the cells that make myelin. So the blue-sky vision is that stem cells could restore some nerve function by replacing missing or faulty cells, or prevent further damage caused by scarring.</p>
<p>Studies in animals have applied stem cells derived from sources including brain tissue, the lining of the nasal cavity, tooth pulp, and embryos (known as embryonic stem cells).</p>
<p>Dramatic improvements have been shown on some occasions, such as <a href="http://www.sciencedirect.com/science/article/pii/S0092867412010185">rats</a> and <a href="http://www.sciencedirect.com/science/article/pii/S1934590916302673">mice</a> regaining bladder control or the ability to walk after injury. While striking, such improvement often represents only a partial recovery. It holds significant promise, but is not direct evidence that such an approach will work in people, particularly those with more complex injuries.</p>
<h2>What is happening now in clinical trials?</h2>
<p>The translation of findings from basic laboratory stem cell research to effective and safe treatments in the clinic involves many steps and challenges. It needs a firm scientific basis from animal studies and then careful evaluation in humans.</p>
<p>Many <a href="https://clinicaltrials.gov/ct2/results?term=stem+cells+AND+spinal+cord+injury&Search=Search">clinical studies</a> examining stem cells for spinal repair are currently underway. The approaches fit broadly into two categories: </p>
<ol>
<li><p>using stem cells as a source of cells to replace those damaged as a result of injury</p></li>
<li><p>applying cells to act on the body’s own cells to accelerate repair or prevent further damage.</p></li>
</ol>
<p>One study that has attracted significant interest involves the injection of myelin-producing cells made from human embryonic stem cells. Researchers hoped that these cells, once injected into the spinal cord, would mature and form a new coating on the nerve cells, restoring the ability of signals to cross the spinal cord injury site. <a href="http://asteriasbiotherapeutics.com/inv_news_listings.php?listing=1392&#asteriasNews">Preliminary results</a> seem to show that the cells are safe; studies are ongoing.</p>
<p>Other clinical trials use cells from patients’ own bone marrow or adipose tissue (fat), or from donated cord blood or nerves from fetal tissue. The scientific rationale is based on the possibility that when transplanted into the injured spinal cord, these cells may provide surrounding tissue with protective factors which help to re-establish some of the connections important for the network of nerves that carry information around the body.</p>
<p>The field as it stands combines <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484454/#B71">years of research</a>, and tens of millions of dollars of investment. However, the development of stem cell therapies for spinal cord injury remains <a href="https://www.christopherreeve.org/research/reeve-stem-cell-research/stem-cell-caution">a long way</a> from translating laboratory promise into proven and effective bedside treatments.</p>
<h2>The promise and uncertainty of ‘breakthroughs’</h2>
<p>Each case is unique in people with spinal cord injury: the level of paralysis, and loss of sensation and function relate to the type of injury and its location. Injuries as a result of stab wounds or infection may result in different outcomes from those incurred as a result of trauma from a car accident or serious fall. The previous health of those injured, the care received at the time of injury, and the type of rehabilitation they access can <a href="https://www.ncbi.nlm.nih.gov/pubmed/25118259">all impact</a> on subsequent health and mobility. </p>
<p>Such variability means caution needs to accompany claims of “man walking again” – particularly when reports relate to a single individual.</p>
<p>In the case that was linked to the Australian of the Year award, the actual 2013 <a href="http://www.ingentaconnect.com/search/article?option2=author&value2=Raisman&operator3=AND&option3=journalbooktitle&value3=Cell+Transplantation&freetype=unlimited&sortDescending=true&sortField=default&pageSize=10&index=1">study</a> focused on whether it was safe to take the patient’s own nerves and other cells from the nose and place these into the damaged region of the spine. While the researchers themselves recommended caution in interpreting the results, accompanying media reports focused on the outcome from just one of the six participants.</p>
<p>While the outcome was significant for the <a href="http://www.bbc.com/news/health-29645760">gentleman involved</a>, we simply do not know whether recovery may have occurred for this individual even without stem cells, given the type of injury (stab wounds), the level of injury, the accompanying rehabilitation that he received or a combination of these factors. It cannot be assumed a similar outcome would be the case for all people with spinal injury.</p>
<h2>We are not there yet – but there is hope</h2>
<p>Finding a way to alleviate the suffering of those with spinal cord injury, and many other conditions, drives the work of thousands of researchers and doctors around the globe. But stem cells are not a “silver bullet” and should not be immune from careful evaluation in clinical trials. </p>
<p>Failure to proceed with caution could actually cause <a href="https://theconversation.com/buyer-beware-the-hidden-cost-of-stem-cell-tourism-5613">harm</a>. For example, a paraplegic woman who was also <a href="https://www.newscientist.com/article/dn25859-stem-cell-treatment-causes-nasal-growth-in-womans-back/">treated</a> with nasal stem cells showed no clinical improvement, and developed a large mucus-secreting tumour in her spine. This case highlights the need for further refinement and assessment in properly conducted clinical trials before nasal stem cells can become part of mainstream medicine.</p>
<p>It’s also worth noting that for spinal cord injury, <a href="https://docs.google.com/spreadsheets/d/11ZF4Ce_ICmI3AoQlzqvrgNRIhDfc9bl8JUlnwU6CP5Y/edit#gid=838467122">trials for recovery of function</a> are not limited to the use of stem cells but include approaches focused on promoting health of surviving nerves (<a href="https://www.ncbi.nlm.nih.gov/pubmed/19597522">neuroprotection</a>), surgery following injury, nerve transfers, electrical stimulation, external physical supports known as <a href="https://clinicaltrials.gov/ct2/show/NCT02202538?term=spinal+cord+injuries&rank=273">exoskeletons</a>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/20025468">nanotechnology</a> and <a href="https://clinicaltrials.gov/ct2/show/NCT01964261?term=spinal+cord+injuries&rank=489">brain-machine interfaces</a>. </p>
<p>Ultimately, determining which of these approaches will improve the lives of people with spinal injury can only be done through rigorous, ethical research.</p><img src="https://counter.theconversation.com/content/72493/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Megan Munsie receives funding from the Australian Research Council. She is affiliated with the International Society for Stem Cell Research, Australasian Society for Stem Cell Research and International Society for Cellular Therapy. </span></em></p><p class="fine-print"><em><span>Andrew Nunn and Claire Tanner do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Claims that stem cell treatments can repair spinal injuries right now are overblown. But it’s not for lack of trying, and the science is certainly progressing.Megan Munsie, Head of Education, Ethics, Law & Community Awareness Unit, Stem Cells Australia, The University of MelbourneAndrew Nunn, Adjunct Research Associate , Monash UniversityClaire Tanner, Postdoctoral research fellow, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/721792017-02-01T23:13:37Z2017-02-01T23:13:37ZWhat’s the benefit in making human-animal hybrids?<figure><img src="https://images.theconversation.com/files/155146/original/image-20170201-12681-90tftv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The red shows rat cells in the developing heart of a mouse embryo.</span> <span class="attribution"><span class="source">Salk Institute</span></span></figcaption></figure><p>A team of scientists from the Salk Institute in the United States created a stir last week with the <a href="http://www.cell.com/cell/fulltext/S0092-8674(16)31752-4">announcement</a> that they had created hybrid human-pig foetuses.</p>
<p>The story was widely reported, although some outlets took a more <a href="https://www.thesun.co.uk/news/2713619/scientists-make-pig-human-babies-by-splicing-stem-cells-in-amazing-new-trial/">hyperbolic</a> or <a href="http://www.lifenews.com/2017/01/27/scientists-create-human-pig-hybrids-for-organ-transplants-that-could-develop-into-monsters/">alarmed</a> tone than <a href="http://www.nature.com/news/hybrid-zoo-introducing-pig-human-embryos-and-a-rat-mouse-1.21378">others</a>.</p>
<p>One might wonder why scientists are even creating human-animal hybrids – often referred to as “<a href="https://www.britannica.com/topic/chimera-genetics">chimeras</a>” after the <a href="https://en.wikipedia.org/wiki/Chimera_(mythology)">Greek mythological creature</a> with features of lion, goat and snake.</p>
<p>The intention is not to create new and bizarre creatures. Chimeras are incredibly useful for understanding how animals grow and develop. They might one day be used to grow life-saving organs that can be transplanted into humans.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=353&fit=crop&dpr=1 600w, https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=353&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=353&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=444&fit=crop&dpr=1 754w, https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=444&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=444&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Jun Wu (front) and Juan Carlos Izpisua Belmonte, who led the team that developed the human-animal chimeras.</span>
<span class="attribution"><span class="source">Salk Institute</span></span>
</figcaption>
</figure>
<h2>Potent cells</h2>
<p>The chimeric pig foetuses produced by <a href="http://www.salk.edu/scientist/juan-carlos-izpisua-belmonte/">Juan Izpisua Belmonte</a>, <a href="http://belmonte.salk.edu/people.php">Jun Wu</a> and their team at the Salk Institute were not allowed to develop to term, and contained human cells in multiple tissues.</p>
<p>The actual proportion of human cells in the chimeras was quite low and their presence appeared to interfere with development. Even so, the study represents a first step in a new avenue of stem cell research which has great promise. But it also raises serious ethical concerns.</p>
<p>A chimera is an organism containing cells from two or more individuals and they do occur in nature, albeit rarely. </p>
<p>Marmoset monkeys often display chimerism in their blood and other tissues as a result of transfer of cells between twins while still in the womb. Following a successful bone marrow transplantation to treat leukaemia, patients have cells in their bone marrow from the donor as well as themselves.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/1hyqzAe0-Q8?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<p>Chimeras can be generated artificially in the laboratory through combining the cells from early embryos of the same or different species. The creation of <a href="http://dev.biologists.org/content/130/25/6155">chimeric mice</a> has been essential for research in developmental biology, genetics, physiology and pathology. </p>
<p>This has been made possible by advances in gene targeting in mouse embryonic stem cells, allowing scientists to alter the cells to express or silence certain genes. Along with the ability to use those cells in the development of chimeras, this has enabled researchers to produce animals that can be used to study how genes influence health and disease. </p>
<p>The pioneers of this technology are Oliver Smithies, Mario Cappechi and Martin Evans, who received a <a href="http://www.nobelprize.org/nobel_prizes/medicine/laureates/2007/">Nobel Prize in Physiology or Medicine in 2007</a> for their work. </p>
<p>More recently, researchers have become interested in investigating the ability of human <a href="http://stemcell.childrenshospital.org/about-stem-cells/pluripotent-stem-cells-101/">pluripotent stem cells</a> – “master cells” – obtained from human embryos or created in the laboratory from body cells, to contribute to the tissues of chimeric animals.</p>
<p>Human pluripotent stem cells can be grown indefinitely in the laboratory, and like their mouse counterparts, they can form all the tissues of the body. </p>
<p>Many researchers have now shown they can make functional human tissues of medical significance from human pluripotent cells, such as nerve, heart, liver and kidney cells. </p>
<p>Indeed, cellular therapeutics derived from human pluripotent stem cells are already in <a href="http://www.nature.com/nrm/journal/v17/n3/full/nrm.2016.10.html">clinical trials</a> for spinal cord injury, diabetes and macular degeneration.</p>
<p>However, since 2007 it has been clear that there is not one type of pluripotent stem cell. Rather, a range of different types of pluripotent stem cells have been generated in mice and humans using different techniques. </p>
<p>These cells appear to correspond to cells at different stages of embryonic development, and therefore are likely to have different properties, raising the question about which source of cells is best.</p>
<p>Creating a chimeras has long been the gold standard used by researchers to determine the potential of pluripotent stem cells. While used extensively in animal stem cell research, chimeric studies using human pluripotent stem cells have proved challenging as few human cells survive in human-animal chimeras.</p>
<h2>Medical possibilities</h2>
<p>Although the number of human cells in the chimera was low, the findings by the Salk Institute researchers provide a new avenue to address two important goals. The first is the possibility of creating “humanised” animals for use in biomedical research. </p>
<p>While it is already possible to produce mice with human blood, providing an invaluable insight into how our blood and immune system functions, these animals rely on the use of human fetal tissue and are difficult to make. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/155149/original/image-20170201-12649-4kcslm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/155149/original/image-20170201-12649-4kcslm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/155149/original/image-20170201-12649-4kcslm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/155149/original/image-20170201-12649-4kcslm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/155149/original/image-20170201-12649-4kcslm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/155149/original/image-20170201-12649-4kcslm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/155149/original/image-20170201-12649-4kcslm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/155149/original/image-20170201-12649-4kcslm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Human iPS cells (green) contributed to a developing heart of four-week-old pig embryo.</span>
<span class="attribution"><span class="source">Salk Institute</span></span>
</figcaption>
</figure>
<p>The use of pluripotent stem cells in human-animal chimeras might facilitate the efficient production of mice with human blood cells, or other tissues such as liver or heart, on a larger scale. This could greatly enhance our ability to study the development of diseases and to develop new drugs to treat them.</p>
<p>The second potential application of human-animal chimeras comes from some <a href="http://www.sciencedirect.com/science/article/pii/S0092867410008433">enticing studies</a> performed in Japan in 2010. These studies were able to generate interspecies chimeras following the introduction of rat pluripotent stem cells into a mouse embryo that lacked a key gene for pancreas development. </p>
<p>As a result, the live born mice had a fully functional pancreas comprised entirely of rat cells. If a similar outcome could be achieved with human stem cells in a pig chimera, this would represent a new source of human organs for transplantation.</p>
<h2>Ethical boundaries</h2>
<p>While scientifically achieving such goals remains a long way off, it is almost certain that progress in pluripotent stem cell biology will enable successful experimentation along these lines. But how much of this work is ethically acceptable, and where do the boundaries lie?</p>
<p>Many people condone the use of pigs for food or as a source of replacement heart valves. They might also be content to use pig embryos and foetuses as incubators to manufacture human pancreas or hearts for those waiting on the transplant list. But the use of human-monkey chimeras may be more contested.</p>
<p>Studies have shown that early cells of the central nervous system made from human embryonic stem cells can <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735209/">engraft and colonise the brain</a> of a newborn mouse. This provides a proof of concept for possible cellular therapies. </p>
<p>But what if human cells were injected into monkey embryos? What would be the ethical and cognitive status of a newborn rhesus monkey whose brain consists of predominantly human nerves?</p>
<p>It may be possible to genetically engineer the cells so that human cells can effectively grow into replacement parts. But what safeguards do we need to ensure that the human cells don’t also contribute to other organs of the host, such as the reproductive organs?</p>
<p>While the announcement of a human-pig chimera may have taken many by surprise, regulators and medical researchers well recognise that chimeric research may raise issues in addition to the those <a href="https://theconversation.com/we-mightnt-like-it-but-there-are-ethical-reasons-to-use-animals-in-medical-research-58878">already posed by animal research</a>.</p>
<p>However, rather than call for a blanket ban or restricting funding for this area of medical research, it requires careful case-by-case consideration by independent oversight committees fully aware of animal welfare considerations and recognising existing standards. </p>
<p>For example, The <a href="http://www.isscr.org/docs/default-source/guidelines/isscr-guidelines-for-stem-cell-research-and-clinical-translation.pdf">2016 Guidelines for Clinical Research and Translation</a> from the International Society for Stem Cell Research call for research where human gametes could be generated from human-animal chimeras to be prohibited, but supports research using human-animal chimeras conducted under appropriate review and oversight.</p>
<p>Chimeric research will and needs to continue. But equally scientists involved in this field need to continue to discuss and consider the implications of their research with the broader community. Chimeras can all too readily be dismissed as mythological monsters engendering fear.</p><img src="https://counter.theconversation.com/content/72179/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Martin Pera receives funding from the Australian Research Council and the National Health and Medical Research Council.</span></em></p><p class="fine-print"><em><span>Megan Munsie receives funding from the Australian Research Council. She is affiliated with the International Society for Stem Cell Research, Australasian Society for Stem Cell Research and International Society for Cell Therapy. </span></em></p>Human-animal hybrids - or ‘chimeras’ - might sound strange, but they offer great hope for new life saving therapies, as long as key ethical boundaries are respected.Martin Pera, Professor and Former Program Leader of Stem Cells Australia, The University of MelbourneMegan Munsie, Head of Education, Ethics, Law & Community Awareness Unit, Stem Cells Australia, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/671922016-10-17T15:00:43Z2016-10-17T15:00:43ZFirst working eggs made from stem cells points to fertility breakthrough<figure><img src="https://images.theconversation.com/files/142020/original/image-20161017-12425-1q4ia8k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Scientists have <a href="http://nature.com/articles/doi:10.1038/nature20104">for the first time</a> shown that fully mature egg cells can be grown in the lab, raising hope for new infertility treatments.</p>
<p>Until now, researchers have only been able to produce cells that resemble sperm or eggs, but which can rarely produce live offspring because of abnormal organisation of their genetic material. But a team at Kyushu University, Japan, have now turned stem cells from mice into mature eggs than can be fertilised and develop into healthy, fertile adults. This could lead to a way for women who can’t naturally produce working eggs to have new ones made from their own cells.</p>
<p><a href="https://stemcells.nih.gov/info/basics/3.htm">Embryonic stem cells</a> are living cells taken from an embryo that have the ability to develop into any other kind of cell. The researchers from Kyushu University team <a href="http://science.sciencemag.org/content/338/6109/971.long">previously demonstrated</a> that, under the right conditions, these cells could be turned into primordial germ cells, immature embryonic versions of sperm and eggs. But because they are immature, these germ cells can’t produce any offspring.</p>
<p>So the researchers <a href="http://nature.com/articles/doi:10.1038/nature20104">adapted their methods</a> to encase the stem cells in other cells taken from a mouse’s foetal gonad (the developing ovary or testis). This recreated an environment more like an ovary and, over a period of four to five weeks, the team saw the stem cells develop into cells resembling mature eggs. </p>
<h2>Fucntioning egg cells</h2>
<p>While the cells looked like mature eggs, the key question was whether they actually were functional egg cells. The team compared their lab-grown eggs with ones from an ovary and found they were the same size and organised their genetic material in similar patterns. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/142021/original/image-20161017-12463-198jm9y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/142021/original/image-20161017-12463-198jm9y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=601&fit=crop&dpr=1 600w, https://images.theconversation.com/files/142021/original/image-20161017-12463-198jm9y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=601&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/142021/original/image-20161017-12463-198jm9y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=601&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/142021/original/image-20161017-12463-198jm9y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=755&fit=crop&dpr=1 754w, https://images.theconversation.com/files/142021/original/image-20161017-12463-198jm9y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=755&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/142021/original/image-20161017-12463-198jm9y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=755&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Mouse embryo.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>The researchers also showed that their eggs could be fertilised, implanted into a surrogate female and go on to produce live offspring. But only a very small number of their embryos created in this way developed fully to term – just 3.5% of all the embryos they transferred. Importantly though, the team reported that “all the obtained pups grew up normally without evidence of premature death.” </p>
<p>As all good scientists should, the researchers then replicated their experiments to test how robust their technique was. Initially, they used embryonic stem cells in their experiments, but these create an ethical dilemma because an embryo has to be destroyed to produce them.</p>
<p><a href="http://www.sciencedirect.com/science/article/pii/S0092867406009767">In 2006</a>, however, another researcher named Shinya Yamanaka and his team found that turning on just four specific genes in normal adult cells gives them all the potential to develop into other cells just like embryonic stem cells, but without the need to destroy a single embryo. The latest research showed that eggs made from these “induced pluripotent stem cells”, or IPSCs, were just as capable of being fertilised and producing healthy adult offspring as embryonic stem cells.</p>
<h2>Research challenges</h2>
<p>The findings from this study have clear implications for the treatment of human infertility. Being able to manufacture working eggs from regular cells could allow doctors to provide an alternative for women who don’t naturally produce functional eggs. But, as with all research studies like this, there are still some limitations that need to be addressed. </p>
<p>First, the overall success rate of this technique is still low – just 3.5% of all embryos implanted gave rise to live offspring, compared to 30% of those currently used for <a href="http://www.hfea.gov.uk/ivf-success-rate.html">human IVF treatment</a>. Obviously, this would need to be improved, potentially by using different lab conditions, hormonal treatments or by encasing the stem cells in adult gonadal cells rather than foetal ones. However, improving the efficiency of such complex lab techniques can be very difficult.</p>
<p>Second, this study was conducted in mice and not humans. While the two species are similar in the way their eggs and embryos develop, there are <a href="http://dev.biologists.org/content/142/18/3090">some key differences</a>. So scientists still need to prove they can replicate the technique with human cells.</p>
<p>Finally, while the researchers went to great lengths to show that the eggs, embryos and offspring generated in this study were “normal”, the lab-grown eggs did display altered genetic patterns and unusual placenta growth. This means we need to research the full impact of the techniques used in this study on the long-term health of any offspring generated.</p>
<p>Still, the findings from this study open up new possibilities for the preservation and even restoration of fertility in women. As always these kinds of scientific breakthroughs, while there are clear benefits for many people, they also carry potential <a href="https://theconversation.com/worlds-first-genetically-modified-human-embryo-raises-ethical-concerns-40766">ethical implications</a>. But the team at Kyushu University have pushed the boundaries of reproductive biology, opening new avenues that may one day help millions.</p><img src="https://counter.theconversation.com/content/67192/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adam Watkins does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Researchers from Kyushu University, Japan, are the first to turn mice stem cells into mature eggs that can be fertilised.Adam Watkins, Research fellow, Cell & Tissue Biomedicine, Aston UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/596812016-09-27T02:18:15Z2016-09-27T02:18:15ZExplainer: what is cystic fibrosis and how is it treated?<figure><img src="https://images.theconversation.com/files/133065/original/image-20160804-478-ravl6f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">CF can’t currently be cured but some emerging treatments show promise. </span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-435851746/stock-photo-portrait-of-young-man-inhaling-through-inhaler-mask.html?src=IFWfunqCGy60N0f8Lk64Aw-1-3">Vadim Zakharishchev/Shutterstock</a></span></figcaption></figure><p>Cystic fibrosis (CF) affects around <a href="https://www.cysticfibrosis.org.au/media/wysiwyg/CF-Australia/PDF_files/40023-ACFDR_Annual_Report_2013vweb.pdf">3,000 people in Australia</a> and <a href="http://www.cysticfibrosisdata.org/LiteratureRetrieve.aspx?ID=149756">70,000 worldwide</a>. It’s an inherited disease caused by a mutation in a single gene called <a href="https://en.wikipedia.org/wiki/Cystic_fibrosis_transmembrane_conductance_regulator">CFTR</a>. </p>
<p>This gene defect means the protein it produces, also called CFTR, is absent or does not function correctly. This disturbs the salt balance in most tubes within the body, including in the airways, gut and the reproductive system.</p>
<h2>What does the gene mutation do?</h2>
<p>Scientists have identified more than <a href="http://www.genet.sickkids.on.ca/StatisticsPage.html">2,000 different mutations</a> in the CFTR gene. These mutations can be separated into <a href="http://www.cftr.info/about-cf/cftr-mutations/the-six-classes-of-cftr-defects/">six different classes</a> that affect how the CFTR protein is produced or functions, and how it affects health.</p>
<p>The CFTR protein is an ion channel that controls salt and water balance. Although many organs in the body are impacted, people with CF are mostly affected by lung disease. The absent or poorly functioning CFTR protein causes the airway to become dehydrated. This results in production of thick sticky mucus that is hard to clear.</p>
<p>The mucus is a perfect breeding ground for bacteria, fungi and viruses. The resulting cycle of infection and inflammation slowly destroys the lung tissue. </p>
<p>Lung function in people with CF gradually and continually worsens, reducing their quality of life and causing early death for many. </p>
<p>Seventy years ago, the average life expectancy of a person born with cystic fibrosis was less than one year. Improvements in care have greatly improved survival to <a href="https://www.cff.org/What-is-CF/About-Cystic-Fibrosis/">around 40 years</a>. These include early detection, better nutrition and enzymes to aid digestion, as well as intensive daily physiotherapy, antibiotics and other drugs to treat lung disease. There is still no cure.</p>
<p>CF has almost become a hidden disease. You may not realise an acquaintance or co-worker has CF until the disease becomes well established and their quality of life deteriorates.</p>
<h2>How is CF lung disease treated?</h2>
<p>CF lung disease cannot currently be cured. Instead, most treatment approaches try to minimise symptoms and slow the progression of lung disease. </p>
<p>One example is <a href="http://www.ncbi.nlm.nih.gov/pubmed/16421364">twice-daily treatment</a> with inhaled hypertonic saline (salty water). This has been used for more than a decade to treat CF lung disease by drawing water onto the airway surface, rehydrating the mucus, and allowing it to clear. Others include daily physiotherapy, which helps to clear mucus, and <a href="https://www.cff.org/Living-with-CF/Treatments-and-Therapies/Inhaled-Medications/Antibiotics/">antibiotics</a>, which treat bacterial infections. </p>
<p>Although CF treatments have improved dramatically over the last decades, most are designed to address the symptoms rather than the cause – the defective CFTR gene present in the cells.</p>
<p>When a person with CF nears the point of lung failure, a lung transplant becomes the only life-saving option. However, suitable donor lungs for transplant are rare and recipients must take daily medications to suppress their immune system so their bodies do not reject the implanted organ. This often produces substantial side-effects, and complications are inevitable. </p>
<p>Currently, <a href="http://www.ncbi.nlm.nih.gov/pubmed/26087666">the five-year survival rate</a> of CF patients following double lung transplant is around 66%. </p>
<p>The disease creates a heavy physical and emotional cost to patients and their families, as well as <a href="http://www.ncbi.nlm.nih.gov/pubmed/23538187">substantial financial cost to the health system</a> and more recently the Pharmaceutical Benefits Scheme (PBS). </p>
<h2>What are genetically focused medicines?</h2>
<p>Genetically focused medicines are a component of <a href="https://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/ps0001_clinical_utility_personalised_medicine_feb_2011.pdf">personalised medicine</a>, in which a diagnostic test to determine a patient’s genetic makeup is used to select an appropriate therapy. Such medicines are beginning to show their real potential for treating CF.</p>
<p>Two new mutation-focused pharmaceuticals are now available. Kalydeco, a drug that improves the defective CFTR protein function, is available on the PBS for the 4% of CF patients with the G551D CFTR mutation. But it’s expensive, currently costing the Australian government <a href="https://www.health.gov.au/internet/ministers/publishing.nsf/Content/health-mediarel-yr2014-dutton092.htm">A$174.5 million over four years</a> (about $300,000 per patient each year). </p>
<p>The other mutation-focused pharmaceutical is Orkambi, a treatment for about 70% of CF patients (those with the F508del CFTR mutation). In April 2016, the Pharmaceutical Benefits Advisory Commission <a href="https://www.pbs.gov.au/industry/listing/elements/pbac-meetings/pbac-outcomes/2016-03/first-time-decisions-not-to-recommend-2016-03.docx">rejected Orkambi</a> on the basis that the A$100 million annual cost was not accompanied by a demonstrated substantial benefit. </p>
<p>Similar rejections of Orkambi have occurred in Ireland and the United Kingdom; Canada has delayed its decision.</p>
<p>Other mutation-specific drugs that restore CFTR function are <a href="https://www.cff.org/Trials/pipeline">in development</a> and in clinical trials. But it’s unclear whether they will be made available to patients through the PBS. </p>
<h2>What is airway gene therapy?</h2>
<p>Another particularly attractive genetically-focused option is gene therapy. This is designed to treat the cause, not the symptoms, of the disease. Airway gene therapy works by delivering a correct copy of the CFTR gene into airway cells to rectify the salt imbalance and improve lung health. </p>
<p>CF is potentially a good target for gene therapies because we probably only need to correct the CFTR gene, unlike cancer in which many genes are implicated and not all are known. The lung is also a relatively accessible organ for delivery.</p>
<p>A <a href="http://www.ncbi.nlm.nih.gov/pubmed/26149841">recent clinical trial in the UK</a> showed that gene therapy was effective for CF lung disease. Monthly deliveries of the CFTR gene inhaled into the airways in small “fatty” globules called liposomes briefly stabilised the decline in lung health in some patients.</p>
<p>A far more efficient method of gene therapy delivery is under development which uses a highly modified and harmless virus as the vehicle that carries in the CFTR gene. </p>
<p>Some viral vectors (carriers) are capable of targeting airway stem cells, the specialised cells of the airway that constantly repair and replenish the cells of the lung. If stem cells are treated, patients might expect lasting benefit as their bodies automatically pass on the correctly functioning CFTR gene to their “daughter” cells. </p>
<p>Such treatment offers hope for lifetime or very long-lived benefits after a single set of treatments. </p>
<p>Importantly, an airway gene therapy of this nature would provide benefits regardless of a person’s CF mutation. </p>
<p>Pre-clinical studies <a href="http://www.ncbi.nlm.nih.gov/pubmed/19634193">look promising</a>, but clinical trials of this method have not yet begun. The <a href="http://www.cfgenetherapy.org.uk/">UK CF Gene Therapy Consortium</a> is preparing for a trial in patients, but the effectiveness and cost are not currently known.</p>
<p>Genetic medicines will undoubtedly be the medicines of our future. But the emergence of effective, potentially curative, but often extraordinarily expensive genetically focused treatments is driving new debate about the cost versus benefit for CF and other diseases, and how these should be funded.</p>
<hr>
<p><em>Update: Since this article was first published, the government has expanded the number of patients eligible to access <a href="https://theconversation.com/weekly-dose-kalydeco-the-drug-that-treats-the-cause-of-cystic-fibrosis-not-just-symptoms-76934">Kalydeco</a> on the Pharmaceutical Benefits Scheme (PBS). The <a href="http://www.health.gov.au/internet/ministers/publishing.nsf/Content/health-mediarel-yr2018-hunt180903.htm?OpenDocument&yr=2018&mth=09">government has also announced</a> Orkambi will be added to the PBS from October 2018.</em></p><img src="https://counter.theconversation.com/content/59681/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Martin Donnelley receives funding from the NHMRC, Women's and Children's Hospital Foundation, Cure4CF Foundation and Australian Synchrotron.</span></em></p><p class="fine-print"><em><span>David Parsons receives research funding from the NHMRC, Cure4CF Foundation SA, the USA CF Foundation, and the Australian Synchrotron.</span></em></p>Cystic fibrosis (CF) affects around 3,000 people in Australia and 70,000 worldwide. It’s an inherited disease caused by a mutation in a single gene called CFTR.Martin Donnelley, Senior research fellow, University of AdelaideDavid Parsons, Chief Medical Scientist and Team Leader, CF Airway Research Group, University of AdelaideLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/658972016-09-22T07:51:04Z2016-09-22T07:51:04ZThe hard sell of stem cells: we need a better way to protect patients from harm<figure><img src="https://images.theconversation.com/files/138746/original/image-20160922-11634-4hxawz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Patients report not being effectively anaesthetised during liposuction procedures to extract stem cells from fat.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-236025184/stock-photo-liposuction-surgery-instrument-prepare-for-operate-in-surgeon-room.html?src=UsnRcoEPIApT4BAYK6X0Mw-1-46">hin255/Shutterstock</a></span></figcaption></figure><p>As <a href="http://www.abc.net.au/news/2016-09-21/stem-cell-marketer-referred-health-ombudsman-over-practices/7864154">ABC’s 7.30</a> revealed last night, Australia has a flourishing stem cell treatment market. During these procedures, cells are taken from a patient and re-administered to them. </p>
<p>These “therapies” are being sold to patients with a wide range of debilitating and chronic conditions with <a href="https://stemcellres.biomedcentral.com/articles/10.1186/scrt543">little or no evidence of benefit</a>. It’s also unclear whether stem cells are even being used in these treatments, despite the advertising claims. </p>
<p>Due to a lack of effective regulations, there is little oversight of these procedures and the businesses that provide them. </p>
<h2>Regulatory loopholes</h2>
<p>Operating in a <a href="https://theconversation.com/cashing-in-on-hope-stem-cell-tourism-risks-arrive-in-our-own-backyard-30827">regulatory loophole</a>, these clinics and businesses are not required to meet the <a href="https://www.tga.gov.au/publication/australian-regulatory-guidelines-biologicals-argb">usual stringent standards</a> required for therapeutic use of cells and tissues in Australia.</p>
<p>In response to concerns about unscrupulous and potentially harmful practices, and after years of inaction, the Therapeutic Goods Administration (TGA) is <a href="https://www.tga.gov.au/consultation/consultation-regulation-autologous-cell-and-tissue-products-and-proposed-consequential-changes-classification-biologicals">currently conducting a public consultation</a> to gauge support for a change in how treatments involving the use of patient’s own cells and tissues are regulated.</p>
<p>Such a review is urgently needed. <a href="http://www.cell.com/cell-stem-cell/fulltext/S1934-5909(16)30210-7">A recent quantitative survey</a> revealed a dramatic increase in the number of Australian clinics marketing and providing these therapies. Australia currently has one of the highest concentrations of clinics per capita. </p>
<p>In the absence of effective regulation, business is booming. But it’s exposing people to unnecessary procedures – just look at <a href="http://www.abc.net.au/news/2016-09-21/stem-cell-marketer-referred-health-ombudsman-over-practices/7864154">the aggressive sales techniques of self-claimed entrepreneurs</a> and the possibility of harm. </p>
<p>Such businesses also run the risk of compromising <a href="https://theconversation.com/stem-cell-therapies-are-advancing-but-will-australian-patients-be-left-behind-56504">legitimate efforts in Australia</a> to translate promising stem cell-based research into effective and safe therapies. </p>
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Read more:
<a href="https://theconversation.com/stem-cell-therapies-are-advancing-but-will-australian-patients-be-left-behind-56504">Stem cell therapies are advancing, but will Australian patients be left behind?</a>
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<h2>Flawed investigation process</h2>
<p>Investigations of medical misconduct or false or misleading advertising are treated on a case-by-case basis after the patient, their family member or medical practitioner make a complaint to the <a href="https://www.tga.gov.au/reporting-problems">TGA</a>, the <a href="http://www.accc.gov.au/consumers/complaints-problems">Australian Competition and Consumer Commission</a> or the <a href="http://www.ahpra.gov.au/Notifications.aspx">Australian Health Practitioner Regulation Agency</a>. </p>
<p>Policing unproven stem cell treatments and their marketing based on this individualised process is problematic for a number of reasons. </p>
<p>Most significantly, it assumes people have the resources, will and empowerment to pursue a complaints process. It also assumes consumers will know which authority to turn to.</p>
<p>People who seek and undergo unproven or experimental stem cell treatment do so for a range of debilitating, often chronic, health conditions. They do so <a href="http://onlinelibrary.wiley.com/doi/10.1111/1467-9566.12092/abstract">in the hope</a> of a better quality of life and for some relief from day-to-day suffering. </p>
<p>They often have more urgent priorities beyond pursuing a complaint after being treated poorly or not getting the outcome they had hoped for. This is especially the case when such treatment has involved feelings of extreme disappointment, embarrassment and disempowerment by an exploitative process.</p>
<p>The family whose experience featured in the <a href="http://www.abc.net.au/news/2016-09-21/stem-cell-marketer-referred-health-ombudsman-over-practices/7864154">7.30 report</a>, for instance, did not wish to formally pursue a complaint despite being subjected to misleading, unethical and exploitative practices. Having raised concerns with <a href="http://www.stemcellsaustralia.edu.au/About-Stem-Cells/For-Patients.aspx">Stem Cells Australia</a>, the peak body representing stem cell science in Australia, they wished to put the unfortunate experience behind them.</p>
<h2>Psychological harm</h2>
<p><a href="http://www.palgrave.com/de/book/9781137470423">Our research</a> indicates that the positive relationship patients forge with their stem cell treatment provider makes it unlikely they will lodge a formal complaint. </p>
<p>In our <a href="http://artsonline.monash.edu.au/research-showcase/high-hopes-high-risk-a-sociological-study-of-stem-cell-tourism/">recent study</a>, people described experiences of harm and concern about their care yet did not act. In addition to the financial difficulties associated with undergoing treatment (procedures generally cost A$9,000), concerns included: </p>
<ul>
<li><p>not being effectively anaesthetised during liposuction procedures to extract stem cells from fat</p></li>
<li><p>experiencing extreme pain and the treating doctor (a cosmetic surgeon) refusing to stop the procedure in spite of repeated requests</p></li>
<li><p>not consenting to what happened to their stem cells after procedures and then being invited to return for subsequent procedures at considerable cost</p></li>
<li><p>concern that stem cells were not administered correctly into sites of injury</p></li>
<li><p>being influenced to undertake procedures due to heavily reduced costs (A$4,000 reduced from A$10,000). </p></li>
</ul>
<p>But patients remained grateful to their “stem cell doctor” despite these experiences. They were happy to have found someone who promised them treatment that could help and who was prepared to do something. </p>
<p>Following the tragic preventable death of Sheila Drysdale, who bled to death following a stem cell treatment for Alzheimer’s disease, the NSW Deputy Coroner ruled that Sheila died as a result of the poor performance of the doctor. </p>
<p>Yet the <a href="http://www.coroners.justice.nsw.gov.au/Pages/findings.aspx#2016%20findings%20and%20recommendations">NSW Coroner’s Report</a> stated Sheila’s husband bore the doctor “no ill-will”. As he explained to <a href="http://www.abc.net.au/radionational/programs/backgroundbriefing/the-life-and-death-of-sheila-drysdale/7641124">ABC’s Background Briefing</a>, he still believed the treatment could have worked: </p>
<blockquote>
<p>Had Sheila survived that night and not bled to death, we may have seen something very positive.</p>
</blockquote>
<p>This story raises concerns ranging from ethical issues associated with lack of informed consent, to physical and psychological harm.</p>
<h2>Diversion from mainstream medicine</h2>
<p>These therapies may also cause harm by diverting people away from effective therapies. </p>
<p>A doctor in Western Australia <a href="http://www.abc.net.au/radionational/programs/backgroundbriefing/2016-07-17/7621838">recently described</a> his serious concern about the harm inflicted on his patient who went off her medication for rheumatoid arthritis in order to undergo an unproven stem cell treatment. </p>
<p>As a result, she experienced a painful and sustained flare-up that may have caused permanent and avoidable damage to her joints. It is unlikely that indirect harms such as these are being reported to authorities.</p>
<p>A reliance on individual consumer complaints to a number of different agencies is an unsatisfactory approach to assessing and addressing harm associated with the exponentially growing Australian unregulated stem cell treatment industry. The TGA consultation closes on October 6. The TGA then needs to act swiftly to introduce meaningful regulatory reform.</p><img src="https://counter.theconversation.com/content/65897/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Claire Tanner receives funding from the Australian Research Council. </span></em></p><p class="fine-print"><em><span>Alan Petersen receives funding from from the ARC. </span></em></p><p class="fine-print"><em><span>Megan Munsie receives funding from the Australian Research Council. She is Head of the Education, Ethics, Law & Community Awareness Unit at Stem Cell Australia. </span></em></p>Due to a lack of effective regulations, there is little oversight of “stem cell treatments” and the businesses that provide them.Claire Tanner, Postdoctoral research fellow, The University of MelbourneAlan Petersen, Professor of Sociology in the School of Social Sciences, Monash UniversityMegan Munsie, Head of Education, Ethics, Law & Community Awareness Unit, Stem Cells Australia, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/542992016-04-13T10:01:43Z2016-04-13T10:01:43ZNew autism research: a nutrient called carnitine might counteract gene mutations linked with ASD risks<figure><img src="https://images.theconversation.com/files/117376/original/image-20160404-27157-4i778m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Deficiencies in a critical nutrient can lead to an abnormally wired brain. Illustration of a network of nerve cells in the
brain.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/wellcomeimages/14665714320/in/photolist-bxvKyF-9RPXGo-okXBVs-btZc25-oAqCtj-9RMzep-a86z8v-a86XrX-btZcaN-oEdnfk-9RM3Ht-9RMx6R-9RQsjq-9RQsgo-btZc41-9RMyGa-9RMzfp-poJjr3-bGTZvH-a89QnE-btZbT7-4QgsFX-4QguVR-4QkHwA-9RMyLx-pEs81t-9RMxmv-bGTZ66-9RQtYo-a86zcZ-btZbJS-a86S6M-9RQuws-a86RTa-9RPVzh-a86zDa-a86PF2-sksaDS-wmwQUS-wmxgKf-9RQtQU-9RMyDr-a86z6K-9RQtTq-aRkaEX-9RMyJ2">Benedict Campbell, Wellcome Images/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span></figcaption></figure><p>Autism spectrum disorders (ASDs) affect about <a href="http://dx.doi.org/10.1001/jamapediatrics.2014.210">one percent</a> of the world’s population. In the United States alone, about <a href="http://dx.doi.org/10.1001/jamapediatrics.2014.210">1 in 68 children</a> are on the spectrum, and between <a href="http://dx.doi.org/10.1001/jamapediatrics.2014.210">40 and 60 percent</a> of them are also diagnosed with some degree of intellectual disability.</p>
<p>The annual cost associated with ASD in the United States is high - presently <a href="http://archpedi.jamanetwork.com/article.aspx?articleid=1879723">estimated to be US$236-$262 billion</a>. If diagnoses continue to grow at the current pace, it will exceed <a href="http://dx.doi.org/10.1007/s10803-015-2521-7">$460 billion by 2025</a>, more than the total cost of diabetes.</p>
<p>Scientists still aren’t sure what causes ASD, but evidence suggests it’s probably the result of complex interactions between genetic and environmental factors that affect brain development. So far hundreds of genes whose mutations are associated with ASD have been identified. Many of them are known or predicted to play critical roles in the cells that make up the building blocks of the brain. </p>
<p>Learning more about these genes – and their mutations – might help us understand some of the root causes of ASD, and perhaps find ways to lower the risk that a child will have it.</p>
<p>We decided to take a closer look at mutations in one of these genes, <a href="http://dx.doi.org/10.1016/j.celrep.2016.01.004">called TMLHE</a>, which is required for a critical chemical reaction that lets cells burn fat molecules to produce energy. We wanted to understand how a TMLHE mutation could increase autism risk and whether we could counteract the effect of the mutation. </p>
<h2>Neural stem cells and the developing brain</h2>
<p>When we examined the effect of TMLHE mutations in mice, we found these mutations specifically affect neural stem cells during early stages of brain development.</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/117371/original/image-20160404-27136-i11h6d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/117371/original/image-20160404-27136-i11h6d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/117371/original/image-20160404-27136-i11h6d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=615&fit=crop&dpr=1 600w, https://images.theconversation.com/files/117371/original/image-20160404-27136-i11h6d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=615&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/117371/original/image-20160404-27136-i11h6d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=615&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/117371/original/image-20160404-27136-i11h6d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=773&fit=crop&dpr=1 754w, https://images.theconversation.com/files/117371/original/image-20160404-27136-i11h6d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=773&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/117371/original/image-20160404-27136-i11h6d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=773&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Stem cells divide in the brain of a zebrafish. A nerve cell (on the outside, turning from purple to white) and another stem cell (on the inside, staying purple), which can itself go on and continue dividing.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/wellcomeimages/25534509980/in/photolist-9RMz1D-EUp3d5">Paula Alexandre, University College London, Wellcome Images/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Neural stem cells create all of the specialized cells that make up the brain. When they divide to create two “daughter” cells, one typically becomes a specialized brain cell, such as a neuron, and the other remains a neural stem cell. </p>
<p>This means that the population of neural stem cells is maintained, and the brain building work can continue. Although this process occurs throughout one’s lifetime, it is the most active during embryonic brain development.</p>
<p>If the neural stem cell population is not maintained at the proper level when the brain is developing, there won’t be enough stem cells left to produce the right number and right kind of specialized brain cells. The result is an abnormally wired brain. </p>
<p>We find this to be precisely the problem that TMLHE mutations created in mice. Too often, neural stem cell division created two specialized cells, instead of one specialized cell and one neural stem cell.</p>
<h2>What does a TMLHE mutation do to neural stem cells?</h2>
<p>TMLHE mutations make it difficult for neural stem cells to produce energy, or to maintain a correctly oxidized environment, which is why they often don’t divide properly. </p>
<p>Cells produce energy by processing fat molecules. For this to happen, fat molecules need to get to the mitochondria, the powerhouses of the cell, to be broken down. A nutrient called carnitine helps transport fat to these parts of the cell.</p>
<p>This is where TMLHE comes in. While we can get carnitine from food – milk and meat, for instance – our bodies can also produce it. But the TMLHE gene is required for carnitine synthesis, so a mutation in this gene can lead to carnitine deficiency. This affects energy production in cells and can also result in a cellular environment that is too oxidized for the cell to function properly, which makes problems for the neural stem cell when it divides.</p>
<p>But we also found that this neural stem cell defect is corrected when carnitine is added to TMLHE-deficient cells. This restores their ability to burn fat into energy and to maintain a proper environment within mitochondria, and restores proper cell division behavior to TMLHE-deficient neural stem cells.</p>
<h2>TMLHE mutations are surprisingly common</h2>
<p>Two recent studies have found that the prevalence of TMLHE mutations in human populations may range from about <a href="http://dx.doi.org/10.1073/pnas.1120210109">1 in 350</a> to about <a href="http://dx.doi.org/10.1038/tp.2012.102">1 in 900</a>. In most cases, these people would be unaware that they carry a copy of the defective gene.</p>
<p>Our research raises the possibility that the increased autism risk associated with TMLHE mutations might be effectively managed by making sure the embryo has enough carnitine during critical stages for brain development. It also seems that sufficient carnitine is required at very early stages of pregnancy – far earlier than previously suspected.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/117374/original/image-20160404-27150-11x4yrm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/117374/original/image-20160404-27150-11x4yrm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/117374/original/image-20160404-27150-11x4yrm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=517&fit=crop&dpr=1 600w, https://images.theconversation.com/files/117374/original/image-20160404-27150-11x4yrm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=517&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/117374/original/image-20160404-27150-11x4yrm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=517&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/117374/original/image-20160404-27150-11x4yrm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=650&fit=crop&dpr=1 754w, https://images.theconversation.com/files/117374/original/image-20160404-27150-11x4yrm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=650&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/117374/original/image-20160404-27150-11x4yrm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=650&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">TLMHE mutations could affect fetal brain development.</span>
<span class="attribution"><a class="source" href="https://upload.wikimedia.org/wikipedia/commons/d/d3/Pregnancy_ultrasound_110322105347_1056300.jpg">Ultrasound via Nevit Dilment via Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Either parent can pass on a defective TMLHE gene. Girls have two copies of the gene, inheriting one from each parent. Boys, however, have only one copy of the gene, which they inherit from the mother. If a male fetus inherits the mutant TMLHE gene, it will be unable to produce its own carnitine and will rely on the mother for its carnitine supply. </p>
<p>Hypothetically, a woman who carries a TMLHE mutation could take supplemental dietary carnitine during pregnancy to try to minimize the associated ASD risk – particularly for male babies. </p>
<h2>Carnitine deficiency may be an underestimated ASD risk</h2>
<p>While hundreds of genes are associated with ASD risk, the surprisingly high incidence of TMLHE mutations in human beings suggests the impact of carnitine deficiency on ASD risk may be badly underestimated. This is a particularly interesting possibility given that diet might be a significant contributing factor to ASD risk associated with TMLHE mutations. </p>
<p>Results from <a href="http://dx.doi.org/10.1016/j.celrep.2016.01.004">our mouse study</a>, and a recent study in which an autistic child with a TMLHE mutation was treated with <a href="http://dx.doi.org/10.1002/ajmg.a.37144">carnitine supplementation</a>, suggest that prenatal carnitine supplementation might well be worth considering. However, more research, particularly clinical trials on human populations, will be needed to further establish the role of carnitine in autism prevention.</p><img src="https://counter.theconversation.com/content/54299/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Vytas A. Bankaitis receives funding from The Robert A. Welch Foundation and the National Institutes of Health. </span></em></p><p class="fine-print"><em><span>Zhigang Xie receives funding from National Institute of Health. </span></em></p>A gene mutation that causes problems for neural stem cells – the building blocks of the brain – could be corrected by adding carnitine.Vytas A. Bankaitis, Professor of Chemistry, Texas A&M Health Science Center, Texas A&M UniversityZhigang Xie, Assistant Research Scientist, Texas A&M Health Science Center, Texas A&M UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/523262015-12-16T15:52:23Z2015-12-16T15:52:23ZHow close are we to successfully editing genes in human embryos?<figure><img src="https://images.theconversation.com/files/106025/original/image-20151215-23205-32o10z.jpg?ixlib=rb-1.1.0&rect=0%2C31%2C639%2C432&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Eight cells in an embryo at three days.</span> <span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/Human_embryogenesis#/media/File:Embryo,_8_cells.jpg">ekem, Courtesy: RWJMS IVF Program/wikimedia</a></span></figcaption></figure><p>An important international summit on human gene editing <a href="http://www.theguardian.com/science/2015/dec/03/gene-editing-summit-rules-out-ban-on-embryos-destined-to-become-people-dna-human">recently recommended</a> that researchers go ahead with gene editing human embryos, but keep revisiting how and when such modifications would be appropriate in the clinic. The decision came after some scientists <a href="http://www.nytimes.com/2015/12/04/science/crispr-cas9-human-genome-editing-moratorium.html?_r=0">called for a moratorium</a> on such research.</p>
<p>The recommendation was always going <a href="https://www.washingtonpost.com/opinions/the-great-potential--and-great-risks--of-gene-editing/2015/12/11/ea1607a4-9a09-11e5-8917-653b65c809eb_story.html">to be controversial</a>, with many people concerned that the technology, which could be used to prevent parents from passing on genetic diseases to their children, will be misused and lead to permanent changes in the human gene pool.</p>
<p>But how close are we – is there really reason to be concerned at this point?</p>
<h2>Laboratory promise</h2>
<p>Gene editing of the human germline – those cells that form the sperm and eggs and, from a fertilised egg, will generate every cell in the human body – is different from other types of genetic editing because changes in those cells will be inherited by future generations, to become a permanent change in the human make-up.</p>
<p>Working on human germline cells at the very earliest stages of the formation of an embryo, just after an egg has been fertilised and then implants itself in the womb, is of course impossible to do in a pregnant woman. In <a href="http://www.gurdon.cam.ac.uk/research/surani">my lab</a>, where our focus is on early development, we approach this research using mice and, more recently, by simply growing human cells in a culture dish. In this way we have managed to identify some of the earliest genetic events that “specify” a stem cell to become a germline cell.</p>
<p>At the same time the technology underpinning gene editing, such as the <a href="https://theconversation.com/explainer-crispr-technology-brings-precise-genetic-editing-and-raises-ethical-questions-39219">CRISPR/Cas9</a> – a fast, easy and unprecedentedly precise method for targeting edits to specific genes – is becoming widespread across science. Together with the new ways of studying germline cells in the lab, this is offering a real chance for scientists and the public to consider whether or not editing of the human germline has merit – before any harm can be done.</p>
<p>We can now <a href="http://dev.biologists.org/content/141/2/245">create human “primordial germ cells”</a>, the precursors to eggs and sperm, from embryonic stem cells. It is a delicate and time-consuming procedure, and the resulting cells do not survive beyond the very early stages of development – partly because we have yet to reproduce the conditions that they are designed to thrive in. What we have been able to show is that some of the earliest steps in the development of human primordial germ cells are [different from those in mice](http://www.cell.com/cell/fulltext/S0092-8674(14). This is important as most of the previous results in this area have come from mouse models, indicating that such information cannot actually be wholly extrapolated to describe humans. </p>
<p>Last year, we also managed to generate primordial <a href="http://www.nature.com/news/rudimentary-egg-and-sperm-cells-made-from-stem-cells-1.16636">germ cells from adult body cells</a>, such as human skin cells. We take body cells that have been programmed to revert back into stem cells, and add chemical factors to “re-specify” them as primordial germ cells.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=593&fit=crop&dpr=1 600w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=593&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=593&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=745&fit=crop&dpr=1 754w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=745&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=745&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">It is possible to create gene-edited sperm in mice. But humans may be a different story.</span>
<span class="attribution"><a class="source" href="https://simple.wikipedia.org/wiki/Semen#/media/File:Sperm-20051108.jpg">Gilberto Santa Rosa from Rio de Janeiro, Brazil/wikimedia</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>While these cells don’t survive long either, experiments have shown that introducing such cells into the testes and ovaries of in mice does allow them to continue their development and maturation into sperm and eggs. Remarkably, such mice were able to <a href="https://www.sciencemag.org/content/338/6109/971.full">give birth to healthy offspring</a> raising the prospect of reprogrammed skin cells creating living human beings. For that reason it certainly makes sense to carry out similar studies using primates. Further research might also make it possible to develop working sperm and egg cells entirely in a culture dish. </p>
<h2>Finished blueprint?</h2>
<p>Looking ahead, it is clear that there already is a potential template for editing the human germline. Genome-sequencing methods could also provide for additional checks to ensure that no inadvertent mutations or “off-target” effects have occurred during the editing procedures. </p>
<p>What’s more, if viable sperm and eggs could be grown in the lab from primordial germ cells, they could be used to generate fertilised embryos. Such “pre-implantation” embryos could also be further screened (as is routine now in the in-vitro fertilisation procedure) to ensure transfer to the womb of only those embryos that are free from specific mutations. </p>
<p>So how could this work in a clinic? Imagine combining the procedures in one patient, for example a woman with a disease-causing mutation who does not wish to pass this mutation to her child. Starting with a cell taken from her skin, this is reprogrammed to a primordial germ cell, in which the DNA is then edited to remove the mutated gene. The primordial germ cell is developed into an egg and used to create an embryo for IVF, to be screened and transplanted back into her womb. The child and its subsequent descendants would be free of the mutated gene.</p>
<p>There’s a reason why the summit carefully considered such massive implications and nevertheless recommended to pursue such research. Without making further gains in our knowledge about the fundamental processes in early germ cell and embryo development – starting with growing germ cells for longer in the culture dish – we will not know what we can and cannot safely achieve with the new gene-editing technologies. We are still some way from being able to contribute the necessary biological evidence to society’s debate about which, if any, of these technologies to pursue.</p><img src="https://counter.theconversation.com/content/52326/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Azim Surani receives funding from The Wellcome Trust and Cancer Research UK</span></em></p>We’re not quite there yet but there is already a potential blueprint for editing the human germline.Azim Surani, Director of Germline and Epigenomics Research at the Gurdon Institute, University of CambridgeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/438942015-09-14T10:14:13Z2015-09-14T10:14:13ZStem cells could help mend a broken heart, but they’ve got to mature<figure><img src="https://images.theconversation.com/files/94437/original/image-20150910-27328-16adew0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Heart cells showing damage after a heart attack.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:MI_with_contraction_bands_very_high_mag.jpg">Nephron</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Heart disease is the <a href="http://www.cdc.gov/heartdisease/facts.htm">number one cause of death</a> in the US. The most common type is coronary heart disease, which occurs when there’s a buildup of plaque within the heart’s blood vessels. <a href="http://www.nhlbi.nih.gov/health/health-topics/topics/hdw/causes">Smoking, diabetes, obesity and high blood pressure</a> can all contribute. When there’s a complete blockage – a heart attack – a large portion of the heart muscle dies. The heart responds by creating scar tissue, eventually leading to heart failure – the heart muscle just can’t pump enough blood to the rest of the body.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=479&fit=crop&dpr=1 600w, https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=479&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=479&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=602&fit=crop&dpr=1 754w, https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=602&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=602&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Blood vessels are blocked with plaque in atherosclerosis.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Coronary_heart_disease-atherosclerosis.PNG">NIH: National Heart, Lung and Blood Institute</a></span>
</figcaption>
</figure>
<p>Currently, the only treatment options for damaged heart muscle are <a href="http://heartsurgery.templehealth.org/content/heart_failure_surgery_transplantation.htm">surgery</a>, if possible, and for the worst cases, a whole heart transplantation. But there’s a <a href="http://www.organdonor.gov/about/data.html">huge shortage of organs</a> for transplantation, and for this reason, we need to find new strategies to treat heart disease.</p>
<p><a href="http://stemcells.nih.gov/info/basics/pages/basics1.aspx">Stem cells</a> have great potential to fill this void. They’re a unique type of cell that starts out unspecialized but can multiply and turn into specialized cells of the adult body – for instance, brain cells or heart muscle cells, officially called cardiomyocytes.</p>
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<span class="caption">A colony of induced pluripotent stem cells under the microscope.</span>
<span class="attribution"><span class="source">Ashley Fong</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p>Stem cells may be useful in tissue engineering therapies; researchers <a href="http://dx.doi.org/10.1016/j.biomaterials.2013.12.052">build tissues from them in the lab</a> to transplant and replace damaged muscle. They could potentially be used in cellular therapies; researchers inject the heart cells into the heart and <a href="http://dx.doi.org/10.1038/nature13233">allow for regeneration</a>. Right now, one <a href="http://capricor.com/clinical-trials/caduceus/">ongoing clinical trial</a> injects a heart attack patient’s own heart stem cells back into the patient’s heart to decrease scar size and promote heart regeneration. In addition, stem cells can also be used as a drug-screening platform in order to find new drugs to treat heart disease.</p>
<p>These options rely on turning stem cells into heart muscle cells – but even once they differentiate, the <a href="http://doi.org/10.1089/scd.2012.0490">heart cells remain immature</a>. They’re not fully developed, having characteristics you’d find in a fetus, not an adult. To advance these possible therapies, we need ways to take these heart muscle cells one step further, to maturity. I’m studying how the heart’s natural environment affects that maturation process. I focus on how the extracellular matrix, or scaffold, of the heart affects maturation. The overall goal is to find a way to create from stem cells fully functioning, mature heart cells that can be safely and effectively used for transplantation therapies and drug screening applications.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/QrNOHKjA2q4?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The author explains her research as part of the UC Grad Slam 2015 at 29:23.</span></figcaption>
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<h2>Adult cells to stem cells to immature heart cells</h2>
<p>There are <a href="http://stemcells.nih.gov/info/basics/pages/basics1.aspx">many kinds of naturally occurring stem cells</a>, but I work with a type that can be made from the adult body. For example, I can take your regular skin cell or blood cell and <a href="http://dx.doi.org/10.1016/j.cell.2007.11.019%20show">transform it in the lab</a> into a stem cell by using viruses to introduce stem cell genes into it. The official name for what I wind up with after three or four weeks is “induced pluripotent stem cells.”</p>
<p>This new stem cell has the unique ability to replicate and turn into almost any cell of the adult body. Since they can be made from a patient’s own cells, the induced pluripotent stem cells retain the patient’s specific genetic information. That’s a big benefit when transplanting the cells – there’s no need for immunosuppression to avoid rejection of the new tissue by the patient’s body. It also allows a patient’s specific disease to be modeled in the lab, in hopes of finding a customized drug or therapy for this individual’s particular disease. This situation is sometimes called a “clinical trial in a dish.”</p>
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<a href="https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The author feeding her cells in the lab.</span>
<span class="attribution"><span class="source">Kimberly Lim</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p>After years of hard work, I was finally successful at manipulating the stem cells into heart muscle cells in the lab. I had to find the perfect stem cell line and protocol to use, which required lots of trial and error. It was very exciting to finally see the beating heart muscle cells in my petri dish!</p>
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<figcaption><span class="caption">Immature cardiomyocytes beating spontaneously in a petri dish.</span></figcaption>
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<p>But the cells’ ability to beat on their own actually demonstrates that they’re immature, and thus shouldn’t be used in treatment and drug screening. They spontaneously beat inappropriately. They don’t have the proper machinery to contract with the necessary force. These actions could have dangerous consequences if we were to rely on immature cells in a patient’s heart. Mature cardiomyocytes beat in response to a signal from the heart’s pacemaker cells, avoiding the safety risk of arrhythmia. And mature cells are strong enough to pump blood throughout the body. </p>
<p>So I need to figure out how to mature these cells. </p>
<h2>Scaffold provides more than just structure</h2>
<p>Within heart tissue, a scaffold surrounds the cells and provides structural support. The tissue is like a brick wall; the bricks are the cells and the mortar is the scaffold of proteins that holds everything together. Just as crucially, in a healthy heart, the scaffold sends signals to the heart cells to behave a specific way that allows them to survive and function normally.</p>
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<a href="https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Cut-up pieces of cow heart with the cells removed, leaving behind the scaffold.</span>
<span class="attribution"><span class="source">Ashley Fong</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
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<p>I obtain the heart scaffold by extracting it from cow hearts. I use detergents to remove the heart cells, similar to how laundry detergent removes dirt from clothes. Once all the cells are removed, only the scaffold remains. It’s made up of a network of fibers consisting of collagen, fibrinogen, elastin and other types of extracellular matrix proteins. After a few more steps, I get the scaffold into the form of a 3D gel – now it has a texture similar to Jello, which I can shape.</p>
<p>When I put my human stem cell-derived heart muscle cell into the adult heart scaffold, it matures. The process works by increasing the amount of some important proteins, including those that handle calcium. That improves calcium signaling, which is essential for the cell to contract.</p>
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<a href="https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The tissue scaffold with the heart muscle cells inside.</span>
<span class="attribution"><span class="source">Ashley Fong</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p>I also discovered that the most maturation occurs when the cells are grown in a 3D scaffold, rather than a 2D scaffold in a traditional flat petri dish. This finding supports the idea that placing the cells in an environment more like their natural habitat can instruct them to develop and mature. We still don’t know how the scaffold actually issues its instructions to the cardiomyocytes to mature, but for now we’re glad it seems to work. </p>
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<a href="https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=457&fit=crop&dpr=1 600w, https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=457&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=457&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=574&fit=crop&dpr=1 754w, https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=574&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=574&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Mature heart muscle cells glowing green with blue nuclei.</span>
<span class="attribution"><span class="source">Ashley Fong</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p>We’re another step closer to being able to use mature stem cell-derived cardiomyocytes in new advanced treatment options to cure heart disease. I’m working on just a small sliver of the type of research that’s needed to get stem cells ready to be used to treat diseases. Stem cell research gives patients and their families hope, but cures won’t happen overnight. Even when we’re not seeing immediate results, stem cell research needs continued support so we researchers can develop the cures we so desperately need.</p><img src="https://counter.theconversation.com/content/43894/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ashley Fong receives funding from the California Institute for Regenerative Medicine, National Science Foundation and National Institute for Health.</span></em></p>Stem cells hold great promise for treating heart disease. But it’s not so simple to get from stem cell to fully functioning adult heart cell, even in the lab.Ashley Fong, PhD Student in Molecular Biology & Biochemistry, University of California, IrvineLicensed as Creative Commons – attribution, no derivatives.