tag:theconversation.com,2011:/fr/topics/tissue-regeneration-8338/articlesTissue regeneration – The Conversation2024-01-09T13:25:50Ztag:theconversation.com,2011:article/2201062024-01-09T13:25:50Z2024-01-09T13:25:50ZI set out to investigate where silky sharks travel − and by chance documented a shark’s amazing power to regenerate its sabotaged fin<figure><img src="https://images.theconversation.com/files/567867/original/file-20240104-19-fvz9ed.jpg?ixlib=rb-1.1.0&rect=0%2C114%2C919%2C596&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Rather than a tracking tag telling scientists where this shark traveled, its violent removal let them observe an unexpected regeneration process.</span> <span class="attribution"><span class="source">Josh Schellenberg</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>I made an accidental and astonishing discovery while studying the movements of sharks off the coast of Jupiter, Florida. I set out to record the migration routes of silky sharks, named for their smooth skin. Instead, in a story filled with twists and turns, I ended up documenting the rare phenomenon of a shark <a href="https://doi.org/10.1155/2023/6639805">regenerating a dorsal fin</a>. </p>
<h2>Tagging, then trauma</h2>
<p>It all started in the summer of 2022, when my team and I tagged silky sharks (<em>Carcharhinus falciformis</em>) as part of my <a href="https://chelsealeighblack.com/research-projects/biotrack/">Ph.D. research</a>. <a href="https://www.floridamuseum.ufl.edu/discover-fish/species-profiles/carcharhinus-falciformis/">Silky sharks</a> are commonly found in the open ocean and grow to be 10 feet long. Scientists know these sharks congregate in South Florida each summer, but where they go the rest of the year remains a mystery – one I hoped to solve. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/567682/original/file-20240103-23-h8z0ck.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Three scientists wearing latex gloves lean over the side of a boat holding a still shark. Woman in middle attaches a hand-sized tag with an short antena to the fin on the shark's back." src="https://images.theconversation.com/files/567682/original/file-20240103-23-h8z0ck.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/567682/original/file-20240103-23-h8z0ck.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=493&fit=crop&dpr=1 600w, https://images.theconversation.com/files/567682/original/file-20240103-23-h8z0ck.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=493&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/567682/original/file-20240103-23-h8z0ck.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=493&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/567682/original/file-20240103-23-h8z0ck.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=620&fit=crop&dpr=1 754w, https://images.theconversation.com/files/567682/original/file-20240103-23-h8z0ck.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=620&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/567682/original/file-20240103-23-h8z0ck.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=620&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Chelsea Black, center, leads a satellite tagging team from the University of Miami in June 2022.</span>
<span class="attribution"><span class="source">Tanner Mansell</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Local boat captain John Moore took us to a site where sharks are known to gather. We carefully caught and gently attached GPS trackers to the dorsal, or top, fin of 10 silky sharks. </p>
<p>The tags, which are attached like large earrings, do not interfere with swimming and are designed to fall off after a few years. When the tag’s antenna breaks the surface of the water, its GPS location is picked up by overhead satellites, hopefully revealing details of the shark’s secret life.</p>
<p>I headed home to track their travels from my laptop. </p>
<p>The story took an unexpected turn a few weeks later, when I received disturbing photos from an avid diver and underwater photographer, Josh Schellenberg, who knew of my work.</p>
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<a href="https://images.theconversation.com/files/567714/original/file-20240103-23-9nlx4h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Silky shark swiming in water with its dorsal fin missing a chunk of tissue shaped like a satellite tag." src="https://images.theconversation.com/files/567714/original/file-20240103-23-9nlx4h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/567714/original/file-20240103-23-9nlx4h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=333&fit=crop&dpr=1 600w, https://images.theconversation.com/files/567714/original/file-20240103-23-9nlx4h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=333&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/567714/original/file-20240103-23-9nlx4h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=333&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/567714/original/file-20240103-23-9nlx4h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=419&fit=crop&dpr=1 754w, https://images.theconversation.com/files/567714/original/file-20240103-23-9nlx4h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=419&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/567714/original/file-20240103-23-9nlx4h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=419&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 first sighting of the wounded silky shark in July 2022.</span>
<span class="attribution"><span class="source">Josh Schellenberg</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>The photos showed a male silky shark with a large, gaping wound in its dorsal fin, as if someone had taken a satellite-tag-shaped cookie cutter and punched it right through. Josh wondered if this individual was one of the sharks from my study. </p>
<p>When placing the GPS tags, I also place a second tag beneath each shark’s dorsal fin that displays a unique ID number, so I was able to confirm the injured shark was one from my study, #409834.</p>
<p>I felt a mixture of relief and sadness. Relief that the shark survived this ordeal; sadness for the scientific data that would now go uncollected. </p>
<p>Silky sharks are often caught by local fishermen in this area but are protected in Florida and <a href="https://myfwc.com/fishing/saltwater/commercial/sharks/">illegal to kill or retain</a>. Josh’s photos of #409834 showed several hooks in his mouth, so I knew this animal had been captured several times since my team tagged him.</p>
<p>The way the satellite tag attaches means it’s impossible for it to naturally rip out of the fin and leave a wound of this shape. Why someone cut off the shark’s satellite tag remains a mystery, but perhaps they thought they could resell it or possibly wanted to interfere with research. I never expected to see that shark again.</p>
<h2>The return of #409834</h2>
<p>Flash forward to one year later, the summer of 2023. I received several photos of silky sharks from John Moore, our boat captain, who is also an avid diver. John was on the lookout for any of our sharks making their seasonal return to Jupiter. In the many shark photos he sent, I noticed a silky shark with an oddly shaped dorsal fin. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/567740/original/file-20240103-15-s905sn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Silky shark swimming through water with an oddly shaped dorsal fin." src="https://images.theconversation.com/files/567740/original/file-20240103-15-s905sn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/567740/original/file-20240103-15-s905sn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/567740/original/file-20240103-15-s905sn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/567740/original/file-20240103-15-s905sn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/567740/original/file-20240103-15-s905sn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/567740/original/file-20240103-15-s905sn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/567740/original/file-20240103-15-s905sn.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>
<figcaption>
<span class="caption">Shark #409834 spotted a year later, in June 2023, with a healed dorsal fin.</span>
<span class="attribution"><span class="source">Josh Schellenberg</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>I knew immediately it had to be #409834 from the previous summer. A few days later, John was able to get close enough to photograph the ID tag to confirm my hunch. Josh Schellenberg also spotted and photographed #409834. With both John’s and Josh’s photos, I was able to compare the healed dorsal fin with the freshly injured one. </p>
<p>I wasn’t expecting to make a groundbreaking discovery. Simple curiosity led me to start analyzing the photos. But the revelation was astonishing: Not only had the wound completely healed, but the 2023 dorsal fin was 10.7% larger in size than it was after the injury in 2022. New fin tissue had regenerated.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/567744/original/file-20240103-29-ocqay6.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A collage of four photos – two are close ups of the dorsal fin freshly injured in 2022 and two are close ups of it healed in 2023. Much of it has grown back." src="https://images.theconversation.com/files/567744/original/file-20240103-29-ocqay6.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/567744/original/file-20240103-29-ocqay6.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=359&fit=crop&dpr=1 600w, https://images.theconversation.com/files/567744/original/file-20240103-29-ocqay6.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=359&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/567744/original/file-20240103-29-ocqay6.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=359&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/567744/original/file-20240103-29-ocqay6.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=451&fit=crop&dpr=1 754w, https://images.theconversation.com/files/567744/original/file-20240103-29-ocqay6.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=451&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/567744/original/file-20240103-29-ocqay6.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=451&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Changes in the dorsal fin from 2022 and 2023.</span>
<span class="attribution"><span class="source">Josh Schellenberg and John Moore</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p><a href="https://doi.org/10.1155/2023/6639805">My analysis</a> determined that within 332 days, the shark regenerated enough tissue that his dorsal fin was almost back to 90% of its original size, growing back more than half of what had been cut off in 2022.</p>
<p>The <a href="https://dlnr.hawaii.gov/sharks/anatomy/fins-swimming/">dorsal fin</a>, pivotal for balance, steering and hydrodynamics, is vital for a shark to be able to hunt and survive. Seeing no infection or any signs of malnourishment in #409834 suggests an extraordinary feat of endurance.</p>
<p>Scientists know that sharks have an incredible <a href="https://doi.org/10.1093/conphys/cov062">aptitude for healing</a> – but mechanisms behind these observations are still poorly understood. While limb regeneration has been widely documented in other marine animals like <a href="https://ssec.si.edu/stemvisions-blog/all-about-starfish">starfish</a> and <a href="https://doi.org/10.1016/j.jembe.2023.151895">crabs</a>, there is only <a href="https://doi.org/10.1093/conphys/coaa120">one other documented case</a> of dorsal fin regeneration in a shark – a whale shark in the Indian Ocean that regrew its dorsal fin after a boat accident in 2006.</p>
<h2>400 million years of resilience</h2>
<p>There’s a reason sharks have been on Earth <a href="https://www.sciencedaily.com/releases/1999/04/990422060147.htm">longer than trees</a> and have survived <a href="https://doi.org/10.1101/2021.01.20.427414">multiple mass extinction events</a> that wiped out other species. They are a product of <a href="https://www.nhm.ac.uk/discover/shark-evolution-a-450-million-year-timeline.html">400 million years</a> of <a href="https://www.floridamuseum.ufl.edu/discover-fish/sharks/fossil/basics/">evolutionary adaptations</a> that demonstrate their remarkable resilience and have primed them for survival.</p>
<p>To be able to pinpoint an ability that helps make them so resilient is a major scientific advance – especially considering scientists are still questioning where silky sharks spend most of their time in the Atlantic. </p>
<p>One person’s attempt to undermine shark science and harm a shark ultimately proved futile. Instead, the shark’s toughness prevailed and led to an amazing discovery about this species. This story also shows there are countless individual people, including scientists like me and shark enthusiasts like Josh and John, who share a genuine love and respect for these animals.</p>
<p>While I’ll never know for certain where #409834 spends the rest of the year, I hope he continues to return to Jupiter each summer so we can further assess his progress. Based on the healing rate calculated in my study, we just might see his dorsal fin grow back to 100% its original size.</p><img src="https://counter.theconversation.com/content/220106/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Chelsea Black does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>After scientists’ GPS tracking tag was violently removed from one shark’s dorsal fin, they were in for a surprise: The wound didn’t just heal, but the missing tissue grew back.Chelsea Black, Ph.D. Candidate in Marine Ecosystems and Society, University of MiamiLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2053732023-07-10T12:32:06Z2023-07-10T12:32:06ZZebrafish share skin-deep similarities with people, making them helpful models to study skin conditions like vitiligo and melanoma<figure><img src="https://images.theconversation.com/files/536160/original/file-20230706-27-zx3jhz.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The melanocytes in zebrafish stripes share many similarities to those in people.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/zebrafish-isolated-on-black-background-royalty-free-image/1134340984">Dan Olsen/iStock via Getty Images Plus</a></span></figcaption></figure><p>Melanocytes are a small subset of epidermal cells that play an outsize role in protecting your skin from the damaging effects of sun exposure. They do this by synthesizing <a href="https://www.ncbi.nlm.nih.gov/books/NBK459156/">melanins, which are pigments</a> sent to other skin cells to shield them from harmful ultraviolet light. A lack of functioning melanocytes causes a <a href="https://doi.org/10.1101/cshperspect.a017046">wide range of skin conditions</a>, including skin cancer and <a href="https://theconversation.com/explainer-what-is-vitiligo-26647">vitiligo, an autoimmune condition</a> in which the body attacks melanocytes and causes patches of depigmented skin. </p>
<p>For nearly 20 years, <a href="https://profiles.umassmed.edu/display/130115">I have been studying</a> melanocytes and the role they play in disease. Difficulties growing human melanocytes <a href="https://theconversation.com/lab-grown-meat-techniques-arent-new-cell-cultures-are-common-tools-in-science-but-bringing-them-up-to-scale-to-meet-societys-demand-for-meat-will-require-further-development-208343">in cell cultures</a> have led researchers like me to use alternative models to study them. </p>
<p><a href="http://www.ceollab.com">My lab</a> and others have pioneered the use of zebrafish to study melanocytes. Using this small freshwater fish as a model organism, my team and I recently discovered a new way in which <a href="https://doi.org/10.7554/eLife.78942">melanocytes regenerate</a>. This process enables flexibility for these cells to recover from injuries and may be applicable to other types of tissues.</p>
<h2>What zebrafish and people have in common</h2>
<p>New students and nonscientists often ask me, “Why zebrafish?” There are several reasons why zebrafish are good models to study melanocytes.</p>
<p>Melanocytes in zebrafish are <a href="https://doi.org/10.1016/j.jid.2021.10.016">similar in many ways</a> to those in people. These cells develop in embryos in the same way those in humans do, use the same genetic programs and make the same melanins. Melanocyte dysfunction in zebrafish also leads to the same diseases and cancers found in people. </p>
<p>Unlike melanocytes in mouse or human skin, zebrafish melanocytes are externally visible in their dark stripes and spotted scales. Researchers can place the whole fish directly under a microscope and see the cells without the need for a biopsy. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/536163/original/file-20230706-21-43u981.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Zebrafish against white background" src="https://images.theconversation.com/files/536163/original/file-20230706-21-43u981.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/536163/original/file-20230706-21-43u981.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=300&fit=crop&dpr=1 600w, https://images.theconversation.com/files/536163/original/file-20230706-21-43u981.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=300&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/536163/original/file-20230706-21-43u981.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=300&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/536163/original/file-20230706-21-43u981.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=377&fit=crop&dpr=1 754w, https://images.theconversation.com/files/536163/original/file-20230706-21-43u981.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=377&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/536163/original/file-20230706-21-43u981.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=377&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Zebrafish melanocytes can be found in their dark stripes and spotted scales.</span>
<span class="attribution"><span class="source">Craig Ceol</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Importantly, researchers can manipulate and perform experiments on zebrafish melanocytes in ways that are unethical or not feasible to do with people. Unlike studies that use isolated melanocytes in a petri dish, these experiments can take place in the context of a whole animal, where we can monitor the surrounding skin and other biological factors for their influence on how melanocytes behave and function.</p>
<h2>Diversity of melanocyte stem cells</h2>
<p>In work spearheaded by <a href="https://www.researchgate.net/scientific-contributions/William-Tyler-Frantz-2121259175">Tyler Frantz</a>, a graduate student in my lab, our team has focused our attention on the process by which new melanocytes <a href="https://doi.org/10.7554/eLife.78942">regenerate after injury</a>.</p>
<p>Melanocyte regeneration is important for recovering from skin disorders such as vitiligo. It’s also relevant to age-related conditions like <a href="https://doi.org/10.1111/brv.12648">hair graying</a>, in which melanocyte stem cells either die or become dormant and no longer produce the mature melanocytes that give hair its color.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/536164/original/file-20230706-21-yzkuvw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Close-up of zebrafish melanocytes -- small dark circles clustered in a band" src="https://images.theconversation.com/files/536164/original/file-20230706-21-yzkuvw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/536164/original/file-20230706-21-yzkuvw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/536164/original/file-20230706-21-yzkuvw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/536164/original/file-20230706-21-yzkuvw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/536164/original/file-20230706-21-yzkuvw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/536164/original/file-20230706-21-yzkuvw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/536164/original/file-20230706-21-yzkuvw.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">The small dark circles clustered in a band across this photo are zebrafish melanocytes, magnified 100 times.</span>
<span class="attribution"><span class="source">Craig Ceol</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>To study melanocyte regeneration, we removed these cells from zebrafish and followed their process of regrowth. Since melanocyte stem cells in zebrafish are externally visible, we tracked these cells in real time to see how they divided and matured. Additionally, we measured which genes were expressed in individual melanocyte stem cells and their descendants during regeneration. </p>
<p>We found that dying melanocytes trigger this regenerative process by sending the signal for melanocyte stem cells – cells that can give rise to new melanocytes – to activate. Surprisingly, we identified two types of stem cells that each took a different route to make new melanocytes. One type of stem cell directly converted into melanin-producing melanocytes. The other type of stem cell divided to create two types of daughter cells. One type was new melanocytes, and the other was new stem cells ready to respond to future injury.</p>
<p>Researchers have known that a single stem cell is capable of <a href="https://doi.org/10.1038/s41580-022-00568-6">making the multiple types of cells</a> needed to regenerate tissue. Our zebrafish studies indicate that multiple different stem cells in skin, and potentially other tissues, can together reconstruct one particular cell type after injury. The involvement of multiple stem cells likely enables regeneration to nimbly adjust to different types of injuries.</p>
<h2>From fish to people</h2>
<p>Our findings from zebrafish are likely relevant to human skin. When we examined cells taken from the <a href="https://doi.org/10.1126/scitranslmed.abd8995">fluid within a blister</a> in human skin, we found cells that look remarkably similar to zebrafish melanocyte stem cells. We are planning to see whether these human cells are activated in skin regeneration to make new melanocytes, which would confirm their identity as melanocyte stem cells. </p>
<p>Ultimately, we envision using these findings to develop treatments that reinvigorate melanocyte stem cells, which could help reverse skin color loss in vitiligo and other diseases. Such treatments may also help counteract age-related pigment loss in hair and skin.</p>
<p>The unique features of zebrafish have allowed us to uncover a new mode of cellular regeneration. Because of cross-species similarities, we expect that these and many other findings from research using zebrafish may be applied to human biology.</p><img src="https://counter.theconversation.com/content/205373/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Craig Ceol receives funding from the National Institutes of Health, US Department of Defense and JW Holdings Pharmaceuticals.</span></em></p>Zebrafish melanocytes cause diseases similar to those in people when they don’t work properly. Studying how they regenerate after injury could lead to new treatments for hair color loss and vitiligo.Craig Ceol, Assistant Professor of Molecular Medicine, UMass Chan Medical SchoolLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1895192022-09-01T18:04:30Z2022-09-01T18:04:30ZAxolotls can regenerate their brains – these adorable salamanders are helping unlock the mysteries of brain evolution and regeneration<figure><img src="https://images.theconversation.com/files/482164/original/file-20220831-8166-9xe77t.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C4096%2C2728&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Axolotls are a model organism researchers use to study a variety of topics in biology.</span> <span class="attribution"><a class="source" href="https://flic.kr/p/aE4bnU">Ruben Undheim/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>The <a href="https://www.nationalgeographic.com/animals/amphibians/facts/axolotl">axolotl</a> (<em>Ambystoma mexicanum</em>) is an aquatic salamander renowned for its ability to <a href="https://doi.org/10.1159%2F000504294">regenerate its spinal cord, heart and limbs</a>. These amphibians also <a href="https://doi.org/10.1186/1749-8104-8-1">readily make new neurons</a> throughout their lives. In 1964, researchers observed that adult axolotls could <a href="https://pubmed.ncbi.nlm.nih.gov/14248567/">regenerate parts of their brains</a>, even if a large section was completely removed. But one study found that axolotl <a href="https://doi.org/10.7554/eLife.13998">brain regeneration</a> has a limited ability to rebuild original tissue structure.</p>
<p>So how perfectly can axolotl’s regenerate their brains after injury? </p>
<p>As a <a href="https://scholar.google.com/citations?user=OdA08uIAAAAJ&hl=en">researcher studying regeneration at the cellular level</a>, I and my colleagues in the <a href="https://bsse.ethz.ch/qdb">Treutlein Lab</a> at ETH Zurich and the <a href="http://tanakalab.org">Tanaka Lab</a> at the Institute of Molecular Pathology in Vienna wondered whether axolotls are able to regenerate all the different cell types in their brain, including the connections linking one brain region to another. In our <a href="https://science.org/doi/10.1126/science.abp9262">recently published study</a>, we created an atlas of the cells that make up a part of the axolotl brain, shedding light on both the way it regenerates and brain evolution across species.</p>
<h2>Why look at cells?</h2>
<p>Different <a href="https://doi.org/10.1038/nrg2416">cell types</a> have different functions. They are able to specialize in certain roles because they each express different genes. Understanding what types of cells are in the brain and what they do helps clarify the overall picture of how the brain works. It also allows researchers to make comparisons across evolution and try to find biological trends across species.</p>
<p>One way to understand which cells are expressing which genes is by using a technique called <a href="https://doi.org/10.3389/fgene.2019.00317">single-cell RNA sequencing (scRNA-seq)</a>. This tool allows researchers to count the number of active genes within each cell of a particular sample. This provides a “snapshot” of the activities each cell was doing when it was collected. </p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/k9VFNLLQP8c?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Single-cell RNA sequencing can provide information on the specific function of each cell in a sample.</span></figcaption>
</figure>
<p>This tool has been instrumental in understanding the types of cells that exist in the brains of animals. Scientists have used scRNA-seq in <a href="https://doi.org/10.1038%2Fnbt.4103">fish</a>, <a href="https://doi.org/10.1126/science.aar4237">reptiles</a>, <a href="https://doi.org/10.1016/j.cell.2018.06.021">mice</a> and even <a href="https://doi.org/10.1126/science.aap8809">humans</a>. But one major piece of the brain evolution puzzle has been missing: amphibians.</p>
<h2>Mapping the axolotl brain</h2>
<p>Our team decided to focus on the <a href="https://doi.org/10.1016/B978-0-323-39632-5.00016-5">telencephalon</a> of the axolotl. In humans, the telencephalon is the largest division of the brain and contains a region called the <a href="https://doi.org/10.1038/nrn2719">neocortex</a>, which plays a key role in animal behavior and cognition. Throughout recent evolution, the neocortex has <a href="https://doi.org/10.3389/fnana.2014.00015">massively grown in size</a> compared with other brain regions. Similarly, the types of cells that make up the telencephalon overall have <a href="https://doi.org/10.1016/j.pneurobio.2020.101865">highly diversified</a> and grown in complexity over time, making this region an intriguing area to study.</p>
<p>We used scRNA-seq to identify the different types of cells that make up the axolotl telencephalon, including different types of <a href="https://www.ninds.nih.gov/health-information/patient-caregiver-education/brain-basics-life-and-death-neuron">neurons</a> and <a href="https://doi.org/10.3389/fnana.2018.00104">progenitor cells</a>, or cells that can divide into more of themselves or turn into other cell types. We identified what genes are active when <a href="https://doi.org/10.3389/fcell.2020.00533">progenitor cells become neurons</a>, and found that many pass through an intermediate cell type called neuroblasts – previously unknown to exist in axolotls – before becoming mature neurons.</p>
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<figcaption><span class="caption">Axolotls’ regenerative abilities have been a source of fascination for scientists.</span></figcaption>
</figure>
<p>We then put axolotl regeneration to the test by removing one section of their telencephalon. Using a <a href="https://doi.org/10.1126/science.aad7038">specialized method of scRNA-seq</a>, we were able to capture and sequence all the new cells at different stages of regeneration, from one to 12 weeks after injury. Ultimately, we found that all cell types that were removed had been completely restored.</p>
<p>We observed that brain regeneration happens in three main phases. The first phase starts with a rapid increase in the number of progenitor cells, and a small fraction of these cells activate a wound-healing process. In phase two, progenitor cells begin to differentiate into neuroblasts. Finally, in phase three, the neuroblasts differentiate into the same types of neurons that were originally lost.</p>
<p>Astonishingly, we also observed that the severed <a href="https://www.brainfacts.org/thinking-sensing-and-behaving/brain-development/2012/making-connections">neuronal connections</a> between the removed area and other areas of the brain had been reconnected. This rewiring indicates that the regenerated area had also regained its original function.</p>
<h2>Amphibians and human brains</h2>
<p>Adding amphibians to the evolutionary puzzle allows researchers to infer how the brain and its cell types has changed over time, as well as the mechanisms behind regeneration.</p>
<p>When we compared our axolotl data with other species, we found that cells in their telencephalon show strong similarity to the mammalian <a href="https://www.ncbi.nlm.nih.gov/books/NBK482171/">hippocampus</a>, the region of the brain involved in memory formation, and the <a href="https://doi.org/10.1016/B978-0-12-801238-3.04706-1">olfactory cortex</a>, the region of the brain involved in the sense of smell. We even found some similarities in one axolotl cell type to the neocortex, the area of the brain known for perception, thought and spatial reasoning in humans. These similarities indicate that these areas of the brain may be evolutionarily conserved, or stayed comparable over the course of evolution, and that the neocortex of mammals may have an ancestor cell type in the telencephalon of amphibians.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Axolotl in tank" src="https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.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>
<figcaption>
<span class="caption">Cracking the mystery of axolotl regeneration could lead to improvements in medical treatments for severe injuries.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Axolotl_ambystoma_mexicanum_anfibio_ASAG.jpg">Amandasofiarana/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>While our study sheds light on the process of brain regeneration, including which genes are involved and how cells ultimately become neurons, we still don’t know what <a href="https://www.nature.com/scitable/topicpage/cell-signaling-14047077/">external signals</a> initiate this process. Moreover, we don’t know if the processes we identified are still accessible to animals that evolved later in time, such as mice or humans.</p>
<p>But we’re not solving the brain evolution puzzle alone. The <a href="https://www.tosches-lab.com/">Tosches Lab</a> at Columbia University explored the diversity of cell types in <a href="https://science.org/doi/10.1126/science.abp9186">another species of salamander, <em>Pleurodeles waltl</em></a>, while the Fei lab at the Guangdong Academy of Medical Sciences in China and collaborators at life sciences company <a href="https://en.genomics.cn/">BGI</a> explored how cell types are <a href="https://science.org/doi/10.1126/science.abp9444">spatially arranged in the axolotl forebrain</a>.</p>
<p>Identifying all the cell types in the axolotl brain also helps pave the way for innovative research in regenerative medicine. The brains of mice and humans have <a href="https://doi.org/10.1100/tsw.2011.113">largely lost their capacity</a> to repair or regenerate themselves. <a href="https://doi.org/10.4103%2F1673-5374.270294">Medical interventions</a> for severe brain injury currently focus on drug and stem cell therapies to boost or promote repair. Examining the genes and cell types that allow axolotls to accomplish nearly perfect regeneration may be the key to improve treatments for severe injuries and unlock regeneration potential in humans.</p><img src="https://counter.theconversation.com/content/189519/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ashley Maynard works at ETH Zurich and has disclosed no relevant affiliations beyond her academic appointment.</span></em></p>Axolotls are amphibians known for their ability to regrow their organs, including their brains. New research clarifies their regeneration process.Ashley Maynard, PhD Candidate in Quantitative Developmental Biology, Swiss Federal Institute of Technology ZurichLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1190112019-08-11T09:09:58Z2019-08-11T09:09:58ZLab studies suggest medicinal plants can help repair human bone and tissue<figure><img src="https://images.theconversation.com/files/287175/original/file-20190807-144838-557nkz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Eucomis autumnalis is more than just a plant - it could play a role in biomedical engineering.</span> <span class="attribution"><span class="source">Gurcharan Singh/Shutterstock</span></span></figcaption></figure><p>There’s been a rise in recent years of biomedical engineering techniques that can restore lost tissue and bone. If you’ve been in a car crash, for instance, there are ways to restore or repair the lost body part or damaged tissues. Sometimes patients will undergo surgical reconstruction; sometimes they’ll be fitted with medical devices such as plates in their knees or hips.</p>
<p>But these approaches have limitations. One is that a steel plate can’t really mimic the functions of damaged tissues or lost bones, so you can lose mobility and flexibility. Another is that these techniques often involve multiple painful operations and long hospital stays. That not only costs the individual patient a lot of time and money; it also places <a href="https://link.springer.com/article/10.1007%2Fs00198-009-0920-3">a burden</a> on a country’s <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048367/">health care system</a> and its economy.</p>
<p>There is an alternative: <a href="https://www.nature.com/subjects/tissue-engineering-and-regenerative-medicine">tissue engineering and regenerative medicine</a>. This process started about three decades ago, and often builds on existing findings to test new approaches. It aims to reactivate biological processes to form products that can help with bone regeneration and tissue loss caused by trauma. </p>
<p>We are among the researchers working in this area. We think that medicinal plants may hold at least some of the answers to the limitations outlined above. We’ve studied two plants commonly used by South African traditional healers and herbalists to treat bone fractures and ease pain caused by osteoarthritis.</p>
<p><a href="https://www.intechopen.com/books/cartilage-tissue-engineering-and-regeneration-techniques/the-potential-effect-of-medicinal-plants-for-cartilage-regeneration">Our studies</a> have yielded positive results in the laboratory. This suggests that compounds drawn from these medicinal plants could offer a valuable way to support bone regeneration and tissue loss in people who’ve suffered trauma.</p>
<h2>How it works</h2>
<p>Tissue engineering and regenerative medicine is based on three key requirements working together: signals from body tissues and organs, responding stem cells, and scaffolds. </p>
<p><a href="https://www.sciencedirect.com/science/article/pii/S136970211170058X">Scaffolds</a> are materials that work with biological systems to evaluate, treat, augment or replace any of the body’s tissues or functions such as mature bone stem cells, cartilage, skin cells, and brain cells and neurons.</p>
<p>These scaffolds are meant to repair or modify cell phase behaviour – that is, how the cells react during development processes such as shape forming. Scaffolds also serve as templates, guiding the development of new tissues by showing them the appropriate route to follow and making sure cells get the nutrients they need. But most of the scaffold biomaterials used in clinical settings don’t tick all of these boxes.</p>
<p>That’s why researchers are looking for alternatives. And that’s where medicinal plants come in. </p>
<h2>Promising plants</h2>
<p>Medicinal plants have long played <a href="https://scialert.net/fulltext/?doi=rjphyto.2010.154.161">an integral role</a> in many cultures. Their role in tissue engineering constructs remains largely unexplored. But given that medicinal plants have been found to have value in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657942/">wound healing</a>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/27956358">pharmaceuticals</a> and ageing therapeutics, it stands to reason that they could be useful in our field, too.</p>
<p>We conducted our research at the Tshwane University of Technology’s department of biomedical sciences in South Africa. The country <a href="https://www.sa-venues.com/plant-life/">is home</a> to one tenth of all the world’s plant species – that’s 25 000 known plant species. We focused on two: <em><a href="http://pza.sanbi.org/eucomis-autumnalis">Eucomis autumnalis</a></em>, commonly called pineapple Lily, and <em><a href="http://pza.sanbi.org/pterocarpus-angolensis">Pterocarpus angolensis</a></em>, or wild teak.</p>
<p>The genus <em>Eucomis autumnalis</em> has been used to heal fractures for centuries. Today it’s often used as a herbal remedy for postoperative recovery and <a href="https://www.researchgate.net/publication/325062906_Possible_roles_of_Eucomis_autumnalis_in_bone_and_cartilage_regeneration_A_review">wound healing</a>. <em>Pterocarpus angolensis</em>, <a href="https://www.ajol.info/index.php/ajtcam/article/viewFile/130696/120273">meanwhile</a>, promotes the formation of cartilage and regulates collagen, which is a substance rich in human bone and cartilage. </p>
<p>We combined these plants with scaffolds and porcine fat cells. We found that the two plants we had identified for laboratory testing activated body cells and enhanced bone formation. They also did a better job of scaffolding when combined with relevant signals and stem cells. And they were good at healing wounds in vitro – that is, in the lab.</p>
<p>Our next step is to carry out our work on animal models and with many other medicinal plants with similar qualities as the ones we used.</p>
<h2>The way forward</h2>
<p>These are exciting findings, because they suggest that incorporating medicinal plants with the relevant properties into biomedical engineering could be a good way to address the limitations of current approaches.</p>
<p>First, using medicinal plants could reduce the cost of treatment because it is economical and easily accessible. Second, it could ensure that patients don’t have to spend as long in hospital after a procedure due to its speeding up of bone formation and cell activation and there’s an added benefit to this line of inquiry: a economic boom for South Africa. </p>
<p>The value of biomedical scaffolding is predicted to reach <a href="https://www.grandviewresearch.com/press-release/global-scaffold-technology-market-analysis">$1.5 billion </a> by 2024. If some of South Africa’s medicinal plants are found to support bone and tissue engineering and regeneration techniques, the country could corner at least part of the global biomaterial market.</p><img src="https://counter.theconversation.com/content/119011/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Franca Nneka Alaribe received funding from National Research Foundation and full Support from Tshwane University of Technology</span></em></p><p class="fine-print"><em><span>This research was funded by the National Research Foundation and Tshwane University of Technology</span></em></p>Tissue engineering and regenerative medicine is based on three key requirements working together: signals from body tissues and organs, responding stem cells, and scaffolds.Franca Nneka Alaribe, Postdoctoral Research Fellow at Biomedical Science Department, Tshwane University of TechnologyKeolebogile Shirley Motaung, Professor of Tissue Engineering, Tshwane University of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1037352018-09-25T15:13:46Z2018-09-25T15:13:46ZWhy older skin heals with less scarring<figure><img src="https://images.theconversation.com/files/237662/original/file-20180924-117383-olicyb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Large scar after surgery on the abdomen young woman.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/scars-removal-concept-large-scar-after-740292784?src=p2QH5MZ6U88TTDQ4BHbDzg-1-30">OneSideProFoto/SHutterstock.com</a></span></figcaption></figure><p>When it comes to your skin, getting older isn’t all bad news. Older people heal skin wounds with thinner scars. </p>
<p>As a practicing dermatologist, my physician colleagues and I make this somewhat counterintuitive observation routinely. But how this occurs is not well understood. Mailyn Nishiguchi, a graduate student, Casey Spencer, a research technician, and I worked together to <a href="https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31340-8">discover how aging normally modulates how our skin heals and the thickness of our scars</a>. </p>
<p><a href="https://www.thomasleunglab.org">My laboratory</a> at the University of Pennsylvania studies how to heal human tissues without a scar. Organisms heal skin wounds using two different processes: scar formation and tissue regeneration. Tissue regeneration results in the return of the original tissue architecture and absence of scars. Scar formation results in fibrous tissue deposition that obliterates the tissue architecture, and generates a thick line of raised red skin. Mammals generally repair injured tissue with scar formation. </p>
<p>In experiments we observed that when young mice were injured, they healed with a scar. However, when elderly mice were injured, their skin wounds regenerated and repaired without a scar. These results reflected what we have observed in our clinic patients. We concluded that aging improves tissue regeneration in both mice and humans, and we set out to understand how this works. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/237560/original/file-20180922-7728-5mjgbh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/237560/original/file-20180922-7728-5mjgbh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=385&fit=crop&dpr=1 600w, https://images.theconversation.com/files/237560/original/file-20180922-7728-5mjgbh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=385&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/237560/original/file-20180922-7728-5mjgbh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=385&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/237560/original/file-20180922-7728-5mjgbh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=483&fit=crop&dpr=1 754w, https://images.theconversation.com/files/237560/original/file-20180922-7728-5mjgbh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=483&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/237560/original/file-20180922-7728-5mjgbh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=483&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Older mice heal skin injuries without a scar.</span>
<span class="attribution"><span class="source">Thomas Leung</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>First, we wanted to see if this change was due to a circulating factor in the blood. We exchanged blood between young and old mice through a technique called parabiosis. When elderly mice were exposed to young blood, their skin no longer regenerated as well. Thus, young blood contained a circulating chemical that promotes scar formation and prevents tissue regeneration from occurring.</p>
<p>To identify this factor, we compared gene activity between injured young and elderly human skin. We focused only on the genes of proteins circulating in the blood and found 13 different proteins in old versus young skin. One of them, SDF1, had previously been shown to regulate tissue regeneration in the <a href="https://doi.org/10.1101/gad.267724.115">skin</a>, <a href="https://doi.org/10.1371/journal.pone.0079768">lung</a> and <a href="https://doi.org/10.1038/nature12681">liver</a>.</p>
<p>To prove that SDF1 may be the mysterious factor responsible for scarring in the young animals, we engineered a mouse that lacked the SDF1 protein in the skin. When SDF1 was eliminated, young mice regenerated their skin with no scarring, just as in elderly mice. Therefore, we concluded that SDF1 promotes scar formation in young mice.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/237757/original/file-20180924-85755-1gdnvey.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/237757/original/file-20180924-85755-1gdnvey.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=249&fit=crop&dpr=1 600w, https://images.theconversation.com/files/237757/original/file-20180924-85755-1gdnvey.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=249&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/237757/original/file-20180924-85755-1gdnvey.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=249&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/237757/original/file-20180924-85755-1gdnvey.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=312&fit=crop&dpr=1 754w, https://images.theconversation.com/files/237757/original/file-20180924-85755-1gdnvey.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=312&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/237757/original/file-20180924-85755-1gdnvey.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=312&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A factor in young blood promotes scar formation.</span>
<span class="attribution"><span class="source">Thomas Leung</span></span>
</figcaption>
</figure>
<p>How does getting older shut off SDF1 production? We discovered that a different protein, called EZH2, turns off the SDF1 gene, and as mice aged, the amount of EZH2 rose. To take this one step further, we used a drug to block EZH2 function in elderly mice. In the absence of EZH2, elderly mice reactivated SDF1 and lost their ability to regenerate their skin.</p>
<p>We wanted to see if these findings also held true in human skin. Similar to mice, skin injury in young people triggered SDF1 production, and this induction was diminished in elderly human skin. We also showed that EZH2 is the reason behind this change. In this case, mouse and human skin behaved in the same way.</p>
<p>Why do mice and humans form more scars when they are young? We speculate that this is a trade-off between speed and quality. Tissue regeneration is a slow process – it takes a month for our skin injuries to regenerate. Meanwhile, a scar can form in little as three to five days. As a young animal, one would want an injury to heal as quickly as possible to live to fight another day. You will tolerate imperfect healing for a faster response. Whereas, older animals that have passed their reproductive prime may not need to heal as fast.</p>
<p>Taken together, we identified a rare example where aging improves tissue function, specifically the tissue repair process. We are planning a clinical trial with the drug, plerixafor, an existing FDA-approved SDF1 inhibitor which is currently used to mobilize stem cells for bone marrow transplant patients, to test its efficacy in preventing scar formation in humans. </p>
<p>Currently, there are no effective treatments on the market to prevent scar formation. In addition to scars from acne and incidental trauma, we hope this approach may be beneficial for many types of human tissue injuries, including the genetic disease epidermolysis bullosa, an extremely debilitating blistering skin disease, in burn patients, or patients with keloid scars.</p><img src="https://counter.theconversation.com/content/103735/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Thomas Leung receives funding from National Institutes of Health, U.S. Department of Veterans Affairs, and the Moseley Foundation. </span></em></p>When kids get injured their skin heals fast, but usually with nasty-looking scars. Now scientists studying the genes of old mice have figured out how they regenerate skin and block scars.Thomas Leung, Assistant Professor of Dermatology, University of PennsylvaniaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/750292017-05-25T08:14:52Z2017-05-25T08:14:52ZStem cells show promise – but they also have a darker side<figure><img src="https://images.theconversation.com/files/167937/original/file-20170504-21635-mqubuo.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-photo/man-knee-pain-over-white-background-575678962?src=Yi25NlrDPOI-pAa0E-b8gA-1-6">Shutterstock</a></span></figcaption></figure><p>Everyone seems to be excited about stem cells. Their excellent promise as a treatment for a range of diseases and injuries mean almost guaranteed coverage for research. While some types of stem cells are already being used in treatment – for treating <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222417/">diseases of the blood and leukaemia</a>, for example, <a href="https://theconversation.com/stem-cells-could-help-treat-multiple-sclerosis-but-its-still-early-days-53413">multiple sclerosis</a> and problems in the bone, skin and eye – there’s still a lot of hype and exaggeration, with some even <a href="https://theconversation.com/the-hard-sell-of-stem-cells-we-need-a-better-way-to-protect-patients-from-harm-65897">selling empty promises</a> to seriously ill or injured patients.</p>
<p>There are many different types of stem cells in the body and they have varying abilities. When most people think of <a href="https://theconversation.com/a-beginners-guide-to-understanding-stem-cells-45502">stem cells</a>, it’s often of embryonic stem cells, which <a href="http://www.eurostemcell.org/embryonic-stem-cell-research-ethical-dilemma">have been controversial</a> for ethical reasons, or their closely related cousins, <a href="http://www.eurostemcell.org/ips-cells-and-reprogramming-turn-any-cell-body-stem-cell">induced pluripotent stem (iPS) cells</a>, adult cells that have been reprogrammed to acquire stem cell-like properties. As the word “pluripotent” suggests, these stem cells have the capacity to transform into any cell type in the body, with the exception of egg and sperm cells. </p>
<p>There are other types of stem cells, however, that are considered to be “multipotent” – not quite as diverse in their abilities as pluripotent stem cells, but still able to turn into different cell types when stimulated <a href="http://www.eurostemcell.org/mesenchymal-stem-cells-other-bone-marrow-stem-cells">in just the right way</a>. These are mesenchymal stem cells, or MSCs, which have the capacity to differentiate into the cell types that give our bodies strength and structure: bones, cartilage, fat, muscle and tendons.</p>
<p>Therapies using MSCs are being touted as a great new hope for the treatment of serious chronic diseases such as colitis, diabetes, arthritis, cirrhosis, kidney disease, heart disease, chronic obstructive pulmonary disorder – <a href="https://link.springer.com/article/10.1007%2Fs00204-014-1232-8">the list goes on and on</a>. In fact, there are currently over 700 MSC-based clinical trials, either ongoing or completed on the <a href="https://clinicaltrials.gov/">clinicaltrials.gov</a> register. </p>
<p>It’s clear why there is so much interest in these cells. But can they really fulfil their promise – and do they have the capacity to harm as well as help us? </p>
<h2>Regeneration and healing</h2>
<p>There are two major promises that have been made when it comes to the use of MSCs in human medicine: their “regeneration potential”, that’s their potential to rebuild damaged tissues, such as bone, spinal cord and heart tissue; and their “healing properties”, which can reverse damage to diseased organs – for example, in arthritis and following organ transplantation.</p>
<p>The regenerative potential of MSCs has been studied since the late 1960s. In <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2613570/">one of the earliest experiments</a> with these cells, Alexander Friedenstein and colleagues showed that transplanting bone marrow to a different site of the body led to bone formation, which indicated that at least some cells in the bone marrow are able to change into bone cells – even in locations where bone would not be expected to grow. </p>
<p>Since then, researchers have worked out different signals that tell MSCs to change into specialised cell types. For example, the growth factor TGF-β can induce MSCs to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840987/">turn into cartilage cells</a>, which would be very helpful in repairing cartilage in arthritis sufferers. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/165905/original/file-20170419-2434-1olj357.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/165905/original/file-20170419-2434-1olj357.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/165905/original/file-20170419-2434-1olj357.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/165905/original/file-20170419-2434-1olj357.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/165905/original/file-20170419-2434-1olj357.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/165905/original/file-20170419-2434-1olj357.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/165905/original/file-20170419-2434-1olj357.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">
<figcaption>
<span class="caption">Mesenchymal stem cells can differentiate into bone, cartilage, muscle and fat cells.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/vculibraries/14061066882/in/photolist-qGEJfq-mhHsTB-pVBh1u-iqknYh-5iqX7N-PeAd2U-gMYr3E-bpDJgr-uGnQbu-useKWk-iBn4N-o3dKej-tMFzaC-usfiDi-tMFzaY-zoYcLE-uJWuok-us6JdA-nHw52Y-cBKU95-uGnuZ3-uJWaN4-uJemSb-yC7hPG-uJW2jF-uJFP6z-uJGoe8-QKf9f8-zDhEww-7BX3K-Qt9FZG-uTxC4r-rkBP7s-GPvStS-nqwDiC-w6RcCA-RobMAi-x3Q29D-zz9L1c-yC7yZC-zhxmzU-xcYXLw-vUs4bu-vUs4c1-sfSdYe-sfS8eP-rYsC6D-paFGmt-pDKwE7-7Y9brF">VCU Libraries/Flikr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Studies are ongoing to determine what signals are needed to transform MSCs into bone to accelerate the healing of fractures, or into cardiac muscle cells to repair the heart after a heart attack. The <a href="http://jamanetwork.com/journals/jama/fullarticle/1388970">POSEIDON</a> and <a href="http://circres.ahajournals.org/content/114/8/1302">PROMETHEUS</a> trials tested the benefits of delivering MSCs directly to the heart after a heart attack. Promisingly, patients who received MSCs in these trials had better heart function and less scar tissue.</p>
<p>Even more ambitious studies are looking into repairing whole organs, <a href="https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-11-171">such as the lung</a>, <a href="http://kjim.org/journal/view.php?doi=10.3904/kjim.2015.30.5.580">liver</a>, and <a href="http://www.fasebj.org/content/29/2/540.long">kidney</a>, which are very susceptible to scar formation (fibrosis) in cases of longstanding inflammation. Needless to say, many of these treatments are still at very early stages, but progress is being made.</p>
<p>The healing properties of MSCs, however, are less clear. MSCs have the ability to move to sites of injury and secrete various factors that promote cell growth, reduce cell death and induce the in-growth of blood vessels in damaged tissue – all <a href="https://stemcellres.biomedcentral.com/articles/10.1186/s13287-016-0353-9">good things</a> that <a href="http://onlinelibrary.wiley.com/doi/10.1111/ejh.12765/abstract">promote healing</a>. Although testing this aspect in chronic disease is still in the early stages, preliminary studies suggest that MSCs are capable of calming inflammation in chronic autoimmune diseases such as <a href="http://journal.frontiersin.org/article/10.3389/fimmu.2017.00462/full">rheumatoid arthritis</a> <a href="http://www.sciencedirect.com/science/article/pii/S0142961215008959">and</a><a href="http://www.sciencedirect.com/science/article/pii/S2211034814001011">multiple sclerosis</a>. </p>
<h2>Scar-forming cells</h2>
<p>One aspect of MSC biology that doesn’t seem to be sufficiently considered when it comes to using these cells for the treatment of human disease is the ability of MSCs to transform into cells we don’t want – scar-forming cells called myofibroblasts. <a href="http://ajplung.physiology.org/content/308/7/L658.long">A number</a> of <a href="https://www.nature.com/articles/ncomms3823">studies</a> in mouse models of lung, liver and kidney fibrosis have shown that the MSCs that normally reside in these tissues – called “pericytes” – quite readily transform into myofibroblasts and produce scar tissue, to the extent that organ function is compromised. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/165857/original/file-20170419-2398-13pzcyk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/165857/original/file-20170419-2398-13pzcyk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=599&fit=crop&dpr=1 600w, https://images.theconversation.com/files/165857/original/file-20170419-2398-13pzcyk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=599&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/165857/original/file-20170419-2398-13pzcyk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=599&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/165857/original/file-20170419-2398-13pzcyk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=753&fit=crop&dpr=1 754w, https://images.theconversation.com/files/165857/original/file-20170419-2398-13pzcyk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=753&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/165857/original/file-20170419-2398-13pzcyk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=753&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">In the lab.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/tareqsalahuddin/7273442826/in/photolist-c5Ji9E-pWiih4-c5JgCA-dQj9Ad-JLTTr-fmSiLd-pqaFaX-e31iwm-afoYQM-bifdrD-9NSJxc-EfoSDV-akmjs3-afoQE4-akiw4T-p3U2Ti-55aheM-jDrQLq-afrUoG-a8Qa4m-afoPwk-afrFts-dvX6v-c5JnXh-afrDgo-afrY9S-afoMqX-afp1Eg-afrCpN-aetqam-afs19S-afoMVr-8o4C7b-afrSp9-aeqBoX-afrNJ7-afrKaq-411wLz-afrMwh-afoTEB-afrDwu-afrDKy-afoTqD-afoUEg-afoY42-8igLZ5-afrPUA-aetq8w-aetqab-afrTwj">Tareq Salahuddin/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>This phenomenon should give us pause, especially when considering the delivery of MSCs into a badly damaged and inflamed part of the body, such as an arthritic joint or the lung of an emphysema patient. </p>
<p>MSCs are exquisitely responsive to their environment, and if these cells are administered to a badly inflamed organ that in turn induces fibrosis, chances are the injected MSCs will transform into myofibroblasts and worsen tissue damage. Clearly, more work needs to be done to find out what signals MSCs will respond to under these conditions, and how these signals will change their biology, for better or for worse.</p>
<p>One of the most important aspects of stem cell treatment that still needs to be considered is their source: will they be taken from the patient who will receive them (not particularly useful for diseases with a strong genetic component) or from a consenting donor (with the added risk of the transplanted cells being rejected)? </p>
<p>Then there is the route of delivery: should MSCs be injected right into the injured/diseased tissue, or administered into the blood and then allowed to move to areas where they are needed? We also need to think about how effective these cells will be, how many cells need to be delivered to have an effect, and how long they stick around in injured tissue. Answers to all of these questions will be needed before we can safely use MSCs in treatment.</p>
<p>Despite the promise, then, there are a number of barriers that need to be surmounted before MSC therapy is a viable treatment and readily available to patients in the clinic. Along with working out the best sources of these cells, the ideal method of delivery, and harnessing their ability to reduce inflammation, we also need to be concerned about controlling the fate of MSCs after they have been administered in order to get the best possible benefit of these cells while not causing further harm.</p><img src="https://counter.theconversation.com/content/75029/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jill Johnson receives funding from the UK Medical Research Council. </span></em></p>Stem cells show potential for treating injuries, but some lab trials show they could be harmful too.Jill Johnson, Lecturer and Principal Investigator, Biosciences, Aston UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/571162016-04-04T20:08:45Z2016-04-04T20:08:45ZRegenerating body parts: how we can transform fat cells into stem cells to repair spinal disc injuries<figure><img src="https://images.theconversation.com/files/117240/original/image-20160404-18648-lw7d5q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Injecting stem cells to repair damaged tissue isn't a new concept, but this method appears safer than others. </span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-394470439/stock-photo-young-girl-with-back-pain-close-up.html?src=1PMDrXUik5Ojl67b6oJDZQ-7-22">Africa Studio/Shutterstock</a></span></figcaption></figure><p>We often hear about the next big thing in stem cell therapy, though few of these promises eventuate or are backed up by evidence. </p>
<p>Well, we think we’re close to a genuine breakthrough in stem cell therapy, based on new research published today in <a href="http://www.pnas.org/">Proceedings of the National Academy of Sciences</a>.</p>
<p>We have developed a stem cell technique capable of regenerating any human tissue damaged by injury, disease or ageing. </p>
<p>The new technique, which reprograms bone and fat cells into <a href="http://www.itek.com.au/portfolio/health/item/small-molecule-induced-neural-stem-cells.html">induced multipotent stem cells</a> (iMS), has successfully repaired bones and muscles in mice. Human trials are set to begin next year.</p>
<h2>How the technique works</h2>
<p>Injecting stem cells to repair damaged tissue is not a new concept. Every time someone receives a bone marrow transplant, they have in fact received blood stem cells to rescue their blood production. </p>
<p>But bone marrow is easy to extract and blood is constantly replaced. Therefore, blood stem cells are relatively easy to source. </p>
<p>This is not the case if you need stem cells to repair damage to muscles, cartilage or organs such as the heart and brain. These stem cells are not easy to extract and their turnover is low.</p>
<p>If stem cells are hard to extract, another option is to reprogram mature cells from other parts of the body that are relatively easy to extract. We have developed a method that converts fat or bone cells, which are relatively easy to extract, into induced multipotent stem cells. </p>
<p>This method involves culturing fat or bone cells with a drug called <a href="http://www.australianprescriber.com/magazine/33/3/89/95/drug/914/azacitidine">Azacitidine</a> and a naturally occurring growth factor called platelet-derived growth factor.</p>
<p>Azacitidine is used to treat blood disorders and has the ability to relax the hard-wired gene expression patterns that make a fat cell a fat cell or a bone cell a bone cell. </p>
<p>We think the combination of erasing the cell’s memory with Azacitidine and forcing the cell to proliferate with the growth factor are key to converting fat and bone cells into induced multipotent stem cells.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/117237/original/image-20160404-18622-1e4p281.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/117237/original/image-20160404-18622-1e4p281.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=848&fit=crop&dpr=1 600w, https://images.theconversation.com/files/117237/original/image-20160404-18622-1e4p281.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=848&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/117237/original/image-20160404-18622-1e4p281.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=848&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/117237/original/image-20160404-18622-1e4p281.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1066&fit=crop&dpr=1 754w, https://images.theconversation.com/files/117237/original/image-20160404-18622-1e4p281.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1066&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/117237/original/image-20160404-18622-1e4p281.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1066&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">UNSW.</span></span>
</figcaption>
</figure>
<h2>The quest for tissue regeneration</h2>
<p>The new technique is similar to the limb regeneration of the salamander, which can repair multiple tissue types, depending on which body part needs replacing.</p>
<p>In 2006, Japanese Nobel Prize-winning stem cell researcher Shinya Yamanaka identified a small number of genes that could reprogram skin cells from mice into immature stem cells, which could grow into all types of cells in the body. </p>
<p>However, these induced pluripotent stem (iPS) cells, like embryonic stem cells, which are derived from early embryos, are not suitable as a stem cell therapy because they can form tumours rather than repairing damaged tissue. </p>
<p>Since then, scientists have identified different combinations of genes that can reprogram skin or other cells into tissue-specific stem cells that only make cells of a single type of tissue. </p>
<p>A drawback with these reprogramming methods is the use of viral elements to force gene expression. Researchers use a virus as a mechanism to inject the gene into the cell. </p>
<p>Multipotent stem cells, in contrast, are produced without using any viral elements. They can regenerate damaged tissues without making unwanted tissues or tumours at the site of transplantation. </p>
<h2>What did we find?</h2>
<p>We have reprogrammed mouse bone cells into induced multipotent stem cells and injected these cells into mice with damaged bone and muscle. </p>
<p>We were astounded by the ability of these induced multipotent stem cells to regenerate these damaged tissues and also generate their own blood supply to carry nutrients to these developing tissues. </p>
<p>The transplanted cells appear to follow instructions from adjacent cells and divide and mature in an orderly fashion.</p>
<h2>Safety and efficacy</h2>
<p>We are still investigating the safety and regenerative potential of human-induced multipotent stem cells. </p>
<p>We have injected human-induced multipotent stem cells, made by reprogramming human fat cells, into our animal models of tissue injury. We are monitoring signals from these cells and know they are retained at the site of injection. </p>
<p>In a few months, we will retrieve tissues from these mice to measure the contribution from transplanted human-induced multipotent stem cells to tissue regeneration in mice.</p>
<p>We need evidence of robust tissue regeneration and the absence of any unwanted tissues or tumours at these sites before commencing human trials.</p>
<h2>Clinical applications</h2>
<p>The process of human induced multipotent stem cell production is free of animal products and is being developed to meet manufacturing standards appropriate for human cell transplantation. </p>
<p>Our initial clinical focus will be using induced multipotent stem cells either as a stand-alone treatment or with spinal implants to treat <a href="http://www.mayfieldclinic.com/PE-DDD.htm">degenerative disc disease</a> towards the end of 2017. </p>
<p>Low back and neck pain is frequently associated with degenerative disc disease and is a major cause of disability, affecting millions of people globally with crippling physical and economic costs.</p>
<p>Our aim is to use induced multipotent stem cells to regenerate discs to retain the flexibility of the native spine or to stabilise spinal implants by helping them fuse with adjacent bone.</p>
<h2>Next steps</h2>
<p>We need further research to understand how mouse- and human-induced multipotent stem cells respond to signals from damaged tissues. It will also be important know how long induced multipotent stem cells remain at sites of transplantation and retain their ability to proliferate and make new tissues. </p>
<p>Nevertheless, this efficient virus-free method of generating tissue regenerative stem cells brings us a step closer to realising stem cell therapy for repairing tissue injury in the human body.</p><img src="https://counter.theconversation.com/content/57116/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Pimanda is employed by UNSW Australia and the Prince of Wales Hospital and receives funding from the National Health and Medical Research Council. </span></em></p><p class="fine-print"><em><span>Vashe Chandrakanthan receives funding from the NHMRC. </span></em></p><p class="fine-print"><em><span>Ralph Mobbs 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>We have developed a new stem cell technique capable of regenerating any human tissue damaged by injury, disease or ageing.John Pimanda, Associate Professor of Medicine and Stem Cell Biology, UNSW SydneyRalph Mobbs, Neurosurgeon at the Prince of Wales Hospital; Conjoint Lecturer, UNSW SydneyVashe Chandrakanthan, Researcher, regenerative medicine, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/233222014-02-17T17:25:42Z2014-02-17T17:25:42ZGenetic switch controls body’s tissue repair system<figure><img src="https://images.theconversation.com/files/41709/original/jsw6zwgf-1392648837.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Those days need not remain in photographs.</span> <span class="attribution"><span class="source">carlos-smith</span></span></figcaption></figure><p>It is a sad fact that old age brings diseases. Many may not be life-threatening, but they make life less fun. One such condition is sarcopenia, which causes the loss of muscle mass and strength, and it is the reason why some old people suffer from loss of stamina, difficulty in walking and heavy breathing.</p>
<p>Sadly there is no treatment for the condition, except for exercise, which only becomes more cumbersome with age. Understanding sarcopenia, then, is crucial to developing new therapies. Now, in a paper published in <a href="http://dx.doi.org/10.1038/nature13013">Nature</a>, scientists have identified the mechanism for this irreversible wear and tear of muscles as one ages.</p>
<p>Our body is made of trillions of cells. Most organs – including the brain, liver, heart, gut and blood vessels – have specialised cells known as adult stem cells, which maintain and repair the organ. The resting state of these cells is “quiescent” – that is, they divide only when required for tissue repair, unlike normal cells that keep dividing throughout their lifetimes. When these adult stem cells are removed or they stop functioning, the body’s repair system stops too. This usually happens with age, leading to degenerative diseases such as sarcopenia.</p>
<p>Now researchers at Pompeu Fabra University, Bellvitge Biomedical Research Institute, and CNIC in Spain have deciphered how stem cells stop working, at least for those found in muscles. By comparing the genes that are turned “on” in muscle stem cells of mice – who act as proxy for humans – the researchers show that the cells of older mice undergo irreversible changes that make them lose their quiescence stage, whereas younger mice are spared the change. Because of this, the potential of muscle stem cells in older mice to self-renew when required is lost too. Instead they switch to being “senescent”, the state in which they cannot divide any more. </p>
<p>Normally senescence is useful. Regardless of how old you are, millions of your body’s cells become senescent every day. One of the functions of senescence is to keep a check on uncontrolled growth of rogue cells that may become cancerous. But senescence becomes more common as we age. And in the case of old people, senescence among stem cells is halting the tissue repair system.</p>
<p>To be sure that it wasn’t the environment causing this response, the researchers extracted muscle stem cells from older mice and implanted them in damaged tissue of younger mice. As expected, the geriatric cells did not repair the tissue, showing that their state was irreversible.</p>
<p>But how exactly do the cells undergo these changes? The researchers found that in old muscle stem cells, the key gene that controls senescence, p16INK4a, is overexpressed – that is, it is switched “on” more than normal. When this gene was not allowed to be expressed, the old cells responded to tissue injury, and replenished the cell population, thereby returning to the quiescence state. The researchers also show that young muscle stem cells repress the production of the gene, which allows them to carry out repair work whenever needed.</p>
<p>The hope would be that, if p16INK4a can be selectively silenced, then this discovery would lead to a treatment for restarting the tissue repair system in old cells. While targeting specific genes in specific cells is not easy, remaining younger and healthier for longer may not always remain that hard.</p>
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<p class="fine-print"><em><span>Mohit Kumar Jolly 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>It is a sad fact that old age brings diseases. Many may not be life-threatening, but they make life less fun. One such condition is sarcopenia, which causes the loss of muscle mass and strength, and it…Mohit Kumar Jolly, Graduate student in Cancer Systems Biology, Rice UniversityLicensed as Creative Commons – attribution, no derivatives.