Communicating About Unproven Stem Cell Treatments to the Public

<p>In recent years, there has been a proliferation of unregulated stem cell clinics providing unproven treatments for patients with a variety of diseases, injuries, and congenital defects. With more than 700 stem cell clinics in operation within the United States alone, and many more worldwide, patients have increasing access to risky, untested options for serious illnesses. As scientists, it is important to effectively communicate the risks of these untested treatments to the public.</p>
<p>I recently attended a lecture at Harvard Medical School on &ldquo;Human Trials: When the Science of Clinical Translation Collides with Stem Cell Tourism.&rdquo; Professors George Daley (Harvard Medical School, USA) and Insoo Hyun, (Case Western Reserve University School of Medicine and Harvard Medical School, USA) spoke to physicians, scientists, and the general public about clinical trials using stem cells, from both clinical and philosophical perspectives. The lecturers attempted to dissect the <em>when&rsquo;s, where&rsquo;s, how&rsquo;s, who&rsquo;s,</em> and <em>why&rsquo;s</em> of experimental medical practice, and the difficulties physician-scientists currently face in a time when stem cell therapies are both promising and uncertain. </p>
<p>It is important that patients understand that there are very few conditions for which stem cell-based therapies have been proven effective and are routinely implemented in medical practice. These are primarily limited to bone marrow stem cell transplantations to treat diseases of the blood and immune system. </p>
<p>Researchers are in the process of testing new stem cell therapies, but any new prospective treatments require clinical trials and a rigorous peer review process before they are accepted as safe and effective. </p>
<p>Emerging cell therapies complicate the traditional system for testing new treatments, however, because &ldquo;Cells are a different type of medicine,&rdquo; explained Dr. Daley. As a result, stem cells currently exist within a grey area of legality for medical regulatory councils within many countries. </p>
<p>This has allowed for-profit stem cell clinics to flourish around the world. These clinics, largely unregulated and unconstrained by ethical guidelines, are thriving, despite the fact that their practices have not been proven to be safe or effective, and in some cases, have caused harm. Individuals who receive unproven stem cell treatments at for-profit clinics are taking on enormous medical and financial risks. </p>
<p>Dr. Hyun explained that these risks do not appear to be strong deterrents as &ldquo;Families under spiritual distress will often seek out dangerous and unproven therapies.&rdquo; </p>
<p>I saw firsthand how the general public seemed unconvinced of the risks and limitations of stem cells, which have been sold to them as miracle cures. Questions raised during the discussion portion by patients and their family members demonstrated that many still considered stem cells to be an infallible, one-size-cures-all medical innovation. From autism to tropical infections, the public appeared to believe that stem cells have unlimited curative properties, despite the risks and complications reported by Drs. Daley and Hyun. Warnings seemed to go largely unheeded. Instead, many hands rose looking for personal referrals. </p>
<p>The communication gap between physicians, scientists, and the general public regarding stem cells and their plausible applications was illustrated to me in that auditorium. I hope future platforms, like this one, are used as an opportunity to share factual evidence with the general public, from the fundamentals of cell biology, to the steps patients and families need to take to avoid becoming victims of a predatory scam. </p>
<p>We do not yet know the full therapeutic spectrum of stem cells, nor their caveats, but it is our responsibility as members of the scientific community to uphold integrity and transparency, and not allow misinformation and anecdotal evidence to out-voice us. </p>
<p>&nbsp;</p>
<p><em>Patients are encouraged to read the </em><a href="https://www.closerlookatstemcells.org/stem-cells-medicine/nine-things-to-know-about-stem-cell-treatments/"><em>Nine Things to Know about Stem Cell Treatments</em></a><em> to learn about the potential and limitations of stem cells, and to detect commonly circulated misinformation</em><em>. </em></p>
<p><a href="https://www.isscr.org/membership/policy/2016-guidelines"><em>International guidelines</em></a><em> were spearheaded by Drs. Daley and Hyun to ensure that stem cell research and clinical trials proceed with scientific and ethical integrity. </em></p>
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<p>Blog by guest contributor Ashlee Conway, PhD, Postdoctoral fellow in the lab of George Daley at Harvard Medical School&rsquo;s Stem Cell Institute &amp; Department of Hematology/Oncology, Boston Children&rsquo;s Hospital, USA</p>

How Understanding Stem Cell Biology Can Improve Cancer Therapy

<p>Radiation therapy and chemotherapy have traditionally been considered the main forms of cancer treatment. While these treatments can be highly effective, they have significant negative side effects due to their unintended collateral toxicity on normal cells in the body. New treatments are needed to more safely treat cancers, which affect millions of people worldwide every year.</p>
<p>In recent years, the world of cancer therapy has rapidly expanded beyond these broad systemic approaches to include immunotherapy (using the body&rsquo;s own immune system to kill cancer cells), targeted therapy (using drugs that target specific genetic mutations), and other forms of precision medicine. However, each of these therapeutic advances comes with their own issues of toxicity and, in some cases, they can stop working if people develop resistance to them. To continue to develop new and innovative therapies for cancers, research into tumor biology is needed. One area of research that holds the potential to provide insight into tumorigenesis is stem cell biology.</p>
<p>The relationship between stem cells, development, and cancer has fascinated scientists for over one hundred years. Stem cells generate or regenerate tissues and organs by multiplying and differentiating into more specialized cell types through highly regulated cell division. This cell division is tightly controlled by specific genes both as people develop in the womb and throughout their lives. However, if the genes regulating cell division become mutated, cells can divide out of control, leading to cancer. Understanding the processes of normal cellular development can help identify effective new targets for cancer therapy.</p>
<p>One major unanswered question in the cancer biology field is regarding how a cancer starts, or what is the cell of origin? Scientists wondered, given that stem cells are mainly responsible for dividing and replenishing many adult tissues, can cancer arise from stem cells?</p>
<p>Supporting this hypothesis, scientists have found that skin and intestinal stem cells are more susceptible to becoming tumors than other cells in those organs. Damage to the network of cells that interact with the stem cells in their &ldquo;niche&rdquo; can also lead to tumor formation. More research is needed to figure out how these changes lead to cancer so that treatments can be developed to specifically stop these cells from dividing out of control.</p>
<p>Understanding stem cell biology can inform cancer treatment even if stem cells aren&rsquo;t the cell of origin. Non-stem cells can hijack the mechanisms used by stem cells to rapidly divide, forming a tumor. These tumor cells use genes that are normally involved in development and stem cell division to initiate aberrant growth.</p>
<p>This phenomenon of cancer cells inappropriately turning on developmental genes to initiate a tumor has been observed in almost every type of cancer and has been modeled in several organisms. Recently, researchers in Leonard Zon&rsquo;s laboratory at Boston Children&rsquo;s Hospital were able to observe this in a living organism, in this case, the well studied zebrafish. For the first time, researchers could watch a <a href="https://vector.childrenshospital.org/2016/01/the-cell-that-caused-melanoma-cancers-surprise-origins-caught-in-action/">single cell become a tumor in a live animal</a>. Scientists discovered that the <a href="https://vector.childrenshospital.org/2016/01/the-cell-that-caused-melanoma-cancers-surprise-origins-caught-in-action/">first event they could observe on the path to melanoma formation</a>, a type of skin cancer, was the re-activation of genes that are otherwise specific to early embryo development. This unique look into the earliest stages of cancer formation allows researchers to screen for new drugs that prevent cancer from forming.</p>
<p>Although the link between stem cells and cancer is strong, more research is needed to determine the cell of origin of different cancer types. If the cell of origin of cancer can be better understood, more specific diagnostic tools and therapies can be developed. Additionally, understanding the genes that control cell division in development and stem cells will hopefully provide new targets to diagnose, treat, and prevent cancer in the future.</p>
<p>___________________________________________________________</p>
<p>Blog by guest contributor Alicia McConnell, PhD, postdoctoral fellow in the lab of Leonard Zon at Boston Children&rsquo;s Hospital, MA, USA.</p>

Injured or Misled by Unscrupulous Stem Cell Clinics? Here’s What You Can Do About It

<p><strong>The Promise</strong></p>
<p>It is all too common today to come across ads declaring that stem cells can cure your [insert disease/condition here]. In fact, these marketing claims made by so-called &ldquo;stem cell" clinics are everywhere: in newspapers, on billboards on your way to and from work, on the television and radio, and littered all over the internet. &ldquo;Suffering and in pain? Have you heard of stem cells? Come by our clinic today&mdash; bring money.&rdquo;</p>
<p><strong>The Reality</strong></p>
<p>In reality, there are currently very few stem cell treatments that are both proven safe and effective and/or approved by regulatory authorities, most of which involve the transplantation blood stem cells (such as bone marrow transplants) to treat certain blood and immune system disorders and some blood cancers. However, this fact has not stopped nefarious stem cell clinics from preying upon suffering and desperate patients by falsely marketing their own stem cell &ldquo;treatment&rdquo; as a silver bullet for any and all diseases, despite the absence of any scientific rationale supporting their approach and evidence of their safety or effectiveness. The growth of unethical stem cell clinics is a <a href="https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(16)30210-7">worldwide phenomenon</a>, including a concentration of <a href="https://www.researchgate.net/publication/325395626_The_US_Direct-to-Consumer_Marketplace_for_Autologous_Stem_Cell_Interventions">716 clinics</a> in the US alone. Importantly, the unproven &ldquo;therapies&rdquo; provided by bad-acting clinics can have exorbitant costs to both your finances and health.</p>
<p><strong>What do you have to lose?</strong></p>
<p>After having undergone unproven stem cell interventions, which can cost thousands of dollars, many patients discover they have not gained any medical benefit to accompany their bill. &nbsp;Even worse, these &ldquo;treatments&rdquo; can have very real negative health repercussions. Numerous adverse events from unproven interventions have been reported in the press, ranging from <a href="https://www.cdc.gov/hai/outbreaks/stem-cell-products.html">mild to severe infections</a>, to <a href="https://www.statnews.com/2017/03/15/stem-cell-patients-blind-macular-degeneration/">blindness</a>, and even tumors (<a href="https://www.statnews.com/2019/07/11/canada-case-long-term-risks-experimental-stem-cell-therapy/">including one on a patient&rsquo;s spine</a>). </p>
<p><strong>What you can do</strong></p>
<p>Importantly, regulatory agencies in countries around the world, including <a href="http://www.isscr.org/professional-resources/news-publicationsss/isscr-news-articles/article-detail/2019/05/21/isscr-applauds-health-canada-s-new-policy-statement-re-autologous-cell-therapy-products">Heath Canada</a><a href="http://www.isscr.org/professional-resources/news-publicationsss/isscr-news-articles/article-detail/2018/04/26/isscr-applauds-australia-s-move-to-regulate-autologous-human-cell-and-tissue-products">, Australia&rsquo;s Therapeutic Goods Administration </a>, and the <a href="http://www.isscr.org/professional-resources/news-publicationsss/isscr-news-articles/article-detail/2019/06/07/isscr-applauds-landmark-court-ruling-in-favor-of-fda-regulating-stem-cell-therapies-offered-by-florida-clinic">US Food and Drug Administration</a>, have strengthened their regulations or <a href="https://www.raps.org/news-and-articles/news-articles/2019/4/fda-to-step-up-stem-cell-enforcement-look-into-pa">stepped up their enforcement</a> of clinics selling unapproved therapies. There are also actions you can take to support these efforts. Whether you have experienced medical harm from these interventions or are simply outraged by the injustice of false marketing claims of stem cell clinics, there are proactive steps <em>you</em> can take to help fight bad acting clinics.</p>
<p><em>Reporting false marketing claims and adverse events to regulatory agencies</em></p>
<p>The ISSCR has recently published an online guide on <a href="https://www.closerlookatstemcells.org/patient-resources/how-to-report-false-marketing-claims-and-adverse-events-from-clinics-offering-unapproved-stem-cell-therapies/">How to Report False Marketing Claims and Adverse Events from Clinics Offering Unapproved Stem Cell &ldquo;Therapies&rdquo;</a> for several countries around the world. This resource includes contact information and direct links for submitting reports to medical regulatory boards, marketing and commercial trade regulators/oversight committees, and governmental health regulators. The list of countries with actionable links will continue to grow. If you have additional actionable links for countries not currently listed on that webpage, you can contact the ISSCR (<a href="mailto:cbarry@isscr.org">cbarry@isscr.org</a>). </p>
<p><em>Make sure you are part of an informed consent process before undergoing treatment</em></p>
<p>Recently, the ISSCR released a <a href="http://www.isscr.org/professional-resources/news-publicationsss/isscr-news-articles/article-detail/2019/08/12/the-isscr-releases-informed-consent-standard-for-stem-cell-based-interventions">Professional Standard for Informed Consent for Stem Cell-Based Interventions</a> meant to help ensure patients know what information should be disclosed to them prior to undergoing unproven stem cell &ldquo;therapies.&rdquo; Specifically, clinicians are required to adequately inform patients about the potential risks and benefits of the procedure before proper informed consent can be given. The new ISSCR standards can be used as a resource to gauge what constitutes proper informed consent and what information should be ethically provided preceding any stem cell-based intervention. </p>
<p><em>Educate yourself and others about red flags of stem cell &ldquo;treatment&rdquo; claims</em></p>
<p>The ISSCR has developed several important resources to help inform the public about the current clinical outlook of stem cell therapies and help spot unproven or unapproved therapies. These resources, located on the <a href="https://www.closerlookatstemcells.org/">A Closer Look at Stem Cells</a> webpage, include <a href="https://www.closerlookatstemcells.org/stem-cells-medicine/stem-cell-treatments-what-to-ask/">What to Ask</a>, <a href="https://www.closerlookatstemcells.org/stem-cells-medicine/nine-things-to-know-about-stem-cell-treatments/">Nine Things to Know About Stem Cell Treatments</a>, the <a href="https://www.closerlookatstemcells.org/patient-resources/">Patient Handbook</a>, and overviews of the current state of stem cell research relevant to <a href="https://www.closerlookatstemcells.org/stem-cells-medicine/">several diseases</a>.</p>
<p>Clinics selling unproven and unapproved stem cell &ldquo;therapies&rdquo; are an international problem and regulatory agencies have had difficulty keeping up, but the momentum is slowly shifting. There is a wave of increasing vigilance against these clinics and enforcing the laws that protect patients from them. And you can help.</p>

Inspirational and Practical Messages from the First ISSCR Women in Science Luncheon

<p>The ISSCR hosted a panel of women at the leading edge of science to share their personal life experiences and discuss how they communicate in fields still largely dominated by men. The discussion, held at the 2019 annual meeting, was extremely inspiring; as a young woman in science, I learned a lot.</p>
<img src="https://www.closerlookatstemcells.org/wp-content/uploads/2019/08/wis-panelresized269125731dff6ddbb37cff0000940c19.tmb-medium.jpg" data-displaymode="Thumbnail" alt="WiS PanelResized" title="WiS PanelResized" style="float: left; margin-left: 10px; margin-right: 10px;" />
<div>
<p>Scientific leaders including Christine Mummery, PhD, <em>Professor of Developmental Biology, Leiden University Medical Center, the Netherlands</em>; Sally Temple, PhD, <em>Neural Stem Cell Institute, USA</em>; Rachel Haurwitz, PhD, <em>President and CEO, Caribou Biosciences, USA</em>; and Laura Mosqueda, MD, <em>Keck School of Medicine, University of Southern California, USA </em>shared stories of their professional careers in academia and industry and their personal lives, childhoods, and families. </p>
<p>Each story uniquely relayed important take-aways, and threads of similarities could be found throughout: experiences of being the only woman in the room, being made to feel that they were too sensitive or were invisible, being talked over and not truly heard, experiencing gender bias and inappropriate behaviors, and being intimidated by men who controlled their careers.</p>
<p>In response to these common experiences, the panelists noted that women often lose self-confidence and decline opportunities. We say &ldquo;no&rdquo; to the opportunity to present at international conferences; we say &ldquo;no&rdquo; to the opportunity to speak up; we say &ldquo;no&rdquo; to the opportunity to take breaks in our careers to start families because we fear losing the high impact papers that define success in science. These observations were disturbing, but resonated with me.&nbsp; </p>
<p>Other common themes focused on the importance of communication. Dr. Mosqueda underscored that leading is about listening carefully and trying to understand different points of view. Dr. Haurwitz stressed the importance of communicating clearly in all settings and taking every opportunity to practice communicating science to others. She also discussed the need to be brave and advocate for yourself and others. Dr. Mummery spoke about the need to lead by example and to remember that when you open a door you should reach back and extend a hand to make sure it is easier for others to follow.</p>
<p>I was also interested in the discussion about how women are often measured by male values of success. Dr. Temple said that &ldquo;As women, we need to define our own ideas for success and rise up when we hit a barrier.&rdquo; Dr. Mosqueda challenged the men in the audience to see what they could learn from women to help improve society. She mentioned the example of different negotiating styles between men and women, with men often asking for more than is needed and women asking only to meet the need; perhaps they could learn from one another. While men can be competitive, the panelists experienced women as more collaborative, working together to lift others up; they suggested that men could learn from women how to be less competitive and more collaborative, less judgmental and more compassionate. In the end, in science as in life, it&rsquo;s all about good communication, listening carefully, and being understanding.</p>
<div>
<p>I agree with the panelists&rsquo; take-home message: women should remember that if you get asked to do something, just do it! Say &ldquo;Yes&rdquo; to opportunities! I am glad I said &ldquo;Yes&rdquo; to the opportunity to join the Women in Science Luncheon and to share my experience with you.<br />
___________________________________________________________</p>
</div>
<p>Blog by guest contributor Elisa Giacomelli, PhD candidate in the lab of Christine Mummery at the Leiden University Medical Center, the Netherlands.</p>
</div>

The Stem Cell Conference Where Even the Smartest People Learn Something

<p><em>This month we are sharing a&nbsp;<a href="https://blog.cirm.ca.gov/2019/06/27/the-stem-cell-conference-where-even-the-smartest-people-learn-something/">blog post from the California Institute for Regenerative Medicine</a>&nbsp;(CIRM). CIRM was created in 2004 with the approval of&nbsp;<a href="https://www.cirm.ca.gov/sites/default/files/files/about_cirm/prop71.pdf">Proposition 71: the California Stem Cell Research and Cures Initiative</a>. The agency has funded 54 clinical trials of potential disease treatments, and in 2020 will be seeking additional funding for stem cell research.</em></p>
<p>At first glance, a scientific conference is not the place you would think about going to learn about how to run a political or any other kind of campaign. But then the&nbsp;<a href="http://www.isscr.org/meetings-events/annual-meetings/isscr-annual-meeting-2019">ISSCR Annual Meeting</a>&nbsp;is not your average conference. And that&rsquo;s why CIRM is there and has been going to these events for as long as we have been around.</p>
<p>For those who don&rsquo;t know, ISSCR is the International Society for Stem Cell Research. It&rsquo;s the global industry representative for the field of stem cell research. It&rsquo;s where all the leading figures in the field get together every year to chart the progress in research.</p>
<p>But it&rsquo;s more than just the science that gets discussed. One of the panels kicking off this year&rsquo;s conference was on &lsquo;Why is it Important to Communicate with Policy Makers, the Media and the Public?&rdquo; It was a wide-ranging discussion on the importance of learning the best ways for the scientific community to explain what it is they do, why they do it, and why people should care.</p>
<p><a href="https://profiles.utsouthwestern.edu/profile/126088/sean-morrison.html">Sean Morrison</a>, a former President of ISSCR, talked about his experience trying to pass a bill in Michigan that would enable scientists to do embryonic stem cell research. At the time CIRM was spending millions of dollars funding scientists in California to create new lines of embryonic stem cells; in Michigan anyone doing the same could be sent to prison for a year. He said the opposition ran a fear-based campaign, lying about the impact the bill would have, that it would enable scientists to create half man-half cow creatures (no, really) or human clones. Learning to counter those without descending to their level was challenging, but ultimately Morrison was successful in overcoming opposition and getting the bill passed.</p>
<p><a href="http://neuralsci.org/about-us/our-team/sally-temple-scientific-director-neural-stem-cell-institute">Sally Temple</a>, of the Neural Stem Cell Institute, talked about testifying to a Congressional committee about the importance of fetal tissue research and faced a barrage of hostile questions that misrepresented the science and distorted her views. In contrast Republicans on the committee had invited a group that opposed all fetal tissue research and fed them a bunch of softball questions; the answers the group gave not only had no scientific validity, they were just plain wrong. Fortunately, Temple says she had done a lot of preparation (including watching two hours Congressional hearings on&nbsp;<a href="https://www.c-span.org/">C-SPAN</a>&nbsp;to understand how these hearings worked) and had her answers ready. Even so she said one of the big lessons she stressed is the need to listen to what others are saying and respond in ways that address their fears and don&rsquo;t just dismiss them.</p>
<p>Other presenters talked about their struggles with different issues and different audiences but similar experiences; how do you communicate clearly and effectively. The answer is actually pretty simple. You talk to people in a way they understand with language they understand. Not with dense scientific jargon. Not with reams of data. Just by telling simple stories that illustrate what you did and who it helped or might help.</p>
<p>The power of ISSCR is that it can bring together a roomful of brilliant scientists from all over the world who want to learn about these things, who want to be better communicators. They know that much of the money for scientific research comes from governments or state agencies, that this is public money, and that if the public is going to continue to support this research it needs to know how that money is being spent.</p>
<p>That&rsquo;s a message CIRM has been promoting for years. We know that communicating with the public is not an option, it&rsquo;s a responsibility. That&rsquo;s why, at a time when the very notion of science sometimes seems to be under attack, and the idea of public funding for that science is certainly under threat, having meetings like this that brings researchers together and gives them access to new tools is vital. The tools they can &ldquo;get&rdquo; at ISSCR are ones they might never learn in the lab, but they are tools that might just mean they get the money needed to do the work they want to.</p>

The Genetic Modification of Humans has (Probably) Occurred – What Now?

<p>Chinese scientist He Jiankui shocked the world in November 2018 when he reported the birth of twin girls born from genetically altered embryos, with another genetically-altered baby on the way. Although this report of genetic modification has not been, and may never be, independently confirmed due to privacy concerns, the birth of the so-called &ldquo;<a href="https://www.statnews.com/2018/11/25/china-first-gene-edited-babies-born/">CRISPR babies</a>,&rdquo; named for the <a href="https://www.closerlookatstemcells.org/2017/04/17/a-crispr-method-for-gene-editing-a-biomedical-breakthrough-from-a-germ/">DNA-editing approach</a> used to alter their genome during the IVF process, has had a seismic impact &nbsp;throughout the scientific community and beyond. </p>
<p>Jiankui&rsquo;s news was met with immediate criticism all corners of the globe. If true, he performed a reckless experiment on humans that violated the international scientific and medical consensus, lacked the proper ethical and regulatory review, and could potentially have significant health consequences for the girls as well as broader consequences for society. Numerous scientific organizations, including the ISSCR, have released <a href="http://www.isscr.org/docs/default-source/policy-documents/isscr-statement-re-human-embryo-genome-modification-january-2019.pdf?sfvrsn=2">statements</a> condemning the clinical application of editing the DNA of human embryos. </p>
<p><strong>Scientific and Ethical Concerns</strong></p>
<p>Ironically, the unexpected announcement occurred during an <a href="http://www.nationalacademies.org/gene-editing/2nd_summit/">international summit on human gene editing</a>, designed to convene experts from a variety of disciplines to debate and discuss the &ldquo;many questions [that] remain about the science, application, ethics, and governance of human genome editing.&rdquo; Since the discovery of CRISPR, the scientific community has recognized the broad medical applications of this approach to correct genetic defects as well as the ethical and societal implications, particularly if and/or when it would be used to correct genetic defects in the embryo. <strong>Genetic changes to the embryo have the potential to be incorporated into all cells, including those that give rise to sperm and eggs (also known as germline cells), and thus the changes could be passed onto future generations</strong>. This is not true for genetic changes to adult cells outside of the gonads.</p>
<p>A host of ethical and societal implications arise when considering the potential to inherit man-made changes to the human embryonic genome. Some are detailed in the <a href="http://nuffieldbioethics.org/project/genome-editing-human-reproduction">recent report from the Nuffield Group</a>, such as: </p>
<ul>
<li>under what circumstances would it be acceptable to edit the human embryonic genome?</li>
<li>what are the human welfare implications of such modifications?</li>
<li>what level of safety and scientific evidence is required before its feasible to go forward with this approach? </li>
</ul>
<p>While the report concludes that there are &ldquo;circumstances in which human genome editing interventions should be permitted,&rdquo; it also states that they should not be done until there is an &ldquo;inclusive societal debate&rdquo; on the issue(s). </p>
<p>In addition to the ongoing, and now intensified, discussions taking place, there are a number of groups working on new initiatives to establish a more rigorous framework and guidelines for this research and its potential clinical application. </p>
<ul>
<li>The World Health Organization has convened an <a href="https://www.who.int/news-room/detail/19-03-2019-who-expert-panel-paves-way-for-strong-international-governance-on-human-genome-editing">Expert Advisory Committee</a> to &ldquo;develop global standards for governance and oversight of human genome editing.&rdquo; Among the topics they are discussing is a central registry on human genome editing &ldquo;in order to create an open and transparent database of ongoing work.&rdquo; </li>
<li>Independently, an <a href="https://www.nature.com/articles/d41586-019-00813-7">international collaboration of scientific academies</a>, the U.S. National Academy of Sciences (NAS),the U.S. National Academy of Medicine (NAM), and the UK Royal Society are leading an international commission to discuss the scientific and regulatory issues around editing human embryos. </li>
<li>An international group of scientists have also issued <a href="https://www.nature.com/articles/d41586-019-00726-5">an international governance framework</a> and along with another group called for a <a href="https://www.asgct.org/global/documents/clinical-germline-gene-editing-letter.aspx">moratorium on any clinical embryonic genome manipulation</a> &ldquo;until serious scientific, societal, and ethical concerns are fully addressed.&rdquo; </li>
<li><a href="https://www.japantimes.co.jp/news/2019/04/21/asia-pacific/science-health-asia-pacific/chinas-top-legislature-draw-tighter-rules-human-gene-embryo-trials/#.XMc0uehKjIV">Individual countries</a> are proposing tightening regulations around gene editing research. </li>
</ul>
<p><strong>Important Potential for Medicine</strong></p>
<p>Gene editing, whether in adult cells or the early embryo, has the potential to change how we treat and think about disease. With the change of a single nucleotide, in some cases, a potentially lethal disease might be cured. Before that happens, however, important scientific and ethical issues must be considered and worked through. He Jiankui&rsquo;s announcement in late 2018 has catapulted these conversations forward, and researchers, clinicians, ethicists, and others are now actively engaged in discussions about whether and how human germline genome editing can responsibly become part of medical treatment. Through the various international working groups, scientific societies like the ISSCR, and individual countries, these issues will be addressed in months to come, with the rest of the world waiting and watching.</p>

Stem Cells for Parkinson’s: Therapy and Tools for a Neurological Disorder

<p><em>This is a guest post from The Michael J. Fox Foundation for Parkinson&rsquo;s Research (MJFF). MJFF is committed to the pursuit of a Parkinson&rsquo;s cure and better quality of life for those living with the disease today. Stem cells are valuable tools in that work, helping develop new therapies and learn more about the disease. Find out more about the work they do at www.michaeljfox.org.</em></p>
<p>Parkinson’s disease is a neurological disorder that affects one in 100 people over age 60. The disease causes a variety of symptoms including motor problems such as tremors, muscle rigidity and slowed movement, and non-motor symptoms of cognitive impairment, mood disorders, and autonomic dysfunction. It is estimated that nearly 1 million people in the United States and more than 6 million worldwide have Parkinson&rsquo;s disease. Current treatments can ease some symptoms, but no available therapies stop or slow the progression of the disease. </p>
<p>Scientists are using stem cells to better understand and treat Parkinson&rsquo;s disease. </p>
<p><strong>Stem Cell Treatments<br />
</strong>In Parkinson&rsquo;s disease (PD), cells that make the chemical messenger dopamine degenerate and die. Introducing new dopamine cells into the brain may help replace what is lost in PD and reduce its symptoms. Such a treatment also could reduce medication side effects. Long-term use of the most commonly prescribed PD medication (levodopa) and progressing disease can lead to dyskinesia or uncontrolled, involuntary movements.</p>
<p>Stem cells can be used in the lab to generate many other types of cells, including dopamine cells. Induced pluripotent stem cells (iPS cells) are derived from adult cells (usually from skin or blood) and can be manipulated to act like stem cells. </p>
<p>In late 2017, researchers in Jun Takahashi, MD, PhD&rsquo;s lab at the Center for iPS Cell Research and Application at Kyoto University in Japan announced that a study transplanting nerve cells made from iPS cells into the brains of pre-clinical models was promising. The grafted cells were able to secrete dopamine and stimulate neurons in the brain. The implanted cells survived for two years, appeared to improve symptoms and did not cause ill side effects. </p>
<p>In July 2018, the Kyoto researchers announced plans to start a clinical trial moving the procedure into humans. Researchers inject dopaminergic progenitor cells &mdash; cells that develop into neurons that produce dopamine &mdash; directly into an area of the brain associated with neural degeneration in Parkinson&rsquo;s disease. The scientists completed the first transplant in October and plan to complete six additional operations by 2022.</p>
<p>In the United States, researchers are looking at other possible therapeutic approaches using stem cells. Lorenz Studer, MD, of Memorial Sloan Kettering Cancer Center, was part of the team that first successfully developed dopamine neurons from human embryonic stem cells. His laboratory is now developing a clinical-grade dopamine neuron cell product made from embryonic stem cells. The cells were successfully grafted in animal models, and the Studer lab will potentially move into human clinical trials in 2019. With backing from MJFF, Ole Isacson MD, PhD, and Penelope Hallet, PhD, of Harvard Medical School are testing other promising stem cell therapeutic approaches using dopamine neurons from iPS cells and embryonic stem cells.</p>
<p><strong>Stem Cells as Tools</strong><br />
Stem cells also can be used to create disease models to learn about the molecular mechanisms of PD and test novel drug molecules.</p>
<p>The National Institute of Neurological Disorders and Stroke at the National Institutes of Health created an open-access repository of engineered stem cells from people with Parkinson&rsquo;s, individuals with genetic mutations associated with PD (with the disease and at risk), and control volunteers. Researchers are using these cells to investigate the process of Parkinson&rsquo;s and the role of genetics. They also may be used to screen potential drug therapies. </p>
<p>The Michael J. Fox Foundation also provides stem cells for scientific projects. The MJFF-sponsored Parkinson&rsquo;s Progression Markers Initiative (PPMI) study makes iPS cells available at no cost to qualified researchers. The study provides more than 130 cell lines from its various cohorts: individuals with PD, control participants, and volunteers at risk for developing PD. When coupled with the deep molecular, clinical, and imaging data collected through PPMI, these cells can be powerful tools for understanding what is different in Parkinson&rsquo;s and how scientists may address that dysfunction with new treatments. </p>
<p><strong>The Future</strong><strong><br />
</strong>Stem cell research could help scientists better define Parkinson&rsquo;s pathology, screen new drugs and develop new treatments. There are challenges to overcome; work is still needed to generate robust cells, in both quality and quantity that can survive and function appropriately in the brain. Scientists are investigating which source of cells (induced pluripotent or embryonic) is most effective and scientists will ensure any treatment is safe before it becomes widespread.</p>
<p>Momentum is building, though, and greater technology and disease understanding is pushing the field toward new treatments.</p>
<p>Learn more about stem cells from the <a href="https://www.michaeljfox.org/understanding-parkinsons/living-with-pd/topic.php?stem-cells">Michael J. Fox Foundation</a> and the <a href="https://www.closerlookatstemcells.org/stem-cells-medicine/parkinsons-disease/">ISSCR</a>.</p>
<br />

How Induced Pluripotency Changed Stem Cell Science

<p>An important achievement in stem cell research was recognized in 2012, when the Nobel Prize in Physiology or Medicine was awarded to two scientists who transformed the field: Shinya Yamanaka and John Gurdon. Together, they received the award for &ldquo;the discovery that mature cells can be reprogrammed to become pluripotent.&rdquo; </p>
<p>The impact of this breakthrough opened myriad possibilities for stem cell research and continues to propel the field forward; both men will be addressing the <a href="http://www.isscr.org/meetings-events/annual-meetings/isscr-annual-meeting-2019/attend/networking-opportunities/women-in-science-luncheon">ISSCR annual meeting, 26-29 June, in Los Angeles, Calif</a>. </p>
<p><strong><span style="text-decoration: underline;">Seeds of Discovery<br />
</span></strong>In the 1960s, the early days of stem cell research, John Gurdon was a student in the U.K. when he began working on cloning &mdash; transplanting the nucleus from the cell of one organism into the egg of another where the nucleus had been removed. His experiments demonstrated that a mature cell, one that was fully differentiated, could revert to an earlier state when introduced into a developing egg, in this case a frog tadpole.</p>
<p>Gurdon&rsquo;s work provided a fundamental paradigm shift for developmental biologists: an adult cell, in an already differentiated state, was not permanently stuck in that state as had been previously thought. In fact, in the right environment, adult cells could revert to an earlier, embryonic cell type that would be capable of giving rise to all the specialized cell types present in an adult organism.</p>
<p>With that new understanding, researchers began working to answer key biological questions that surfaced from those early experiments: what genetic, biological, or chemical components were responsible for encouraging cells to go back to an earlier state and regain the potential to become any cell type? What minimal factors would be sufficient to readily reprogram cells? How could reprogramming events be harnessed to better understand human development in health and disease?</p>
<p><strong><span style="text-decoration: underline;">Answering Questions about Cell Development<br />
</span></strong>It wasn&rsquo;t until more than 40 years after Gurdon&rsquo;s work that Shinya Yamanaka and his colleagues in Japan identified the key genes that control this &ldquo;reprogramming&rdquo; of adult cells. Yamanaka was able to induce adult mouse cells to a pluripotent state whereby the cells mimicked <a href="https://www.closerlookatstemcells.org/learn-about-stem-cells/types-of-stem-cells/#embryonic">embryonic stem cells</a> and could become any cell type in the body. These cells are known as &lsquo;<a href="https://www.closerlookatstemcells.org/patient-resources/resources-from-isscr/stem-cell-glossary/#ips-cells">induced pluripotent stem&rsquo;</a> (iPS) cells.</p>
<p>Soon, Yamanaka and another scientist, James Thomson in the U.S., published studies showing that human cells could be similarly reprogrammed back to a pluripotent state. Yamanaka and his team identified just four genes that, if expressed in adult skin cells, could convert mature cells back into <a href="https://www.closerlookatstemcells.org/patient-resources/resources-from-isscr/stem-cell-glossary/#pluripotent-stem-cells">pluripotent stem cells</a> that could become any cell in the body.</p>
<p>Collectively, the research by Gurdon and Yamanaka ushered in a new era that changed the face of stem cell research.</p>
<p><strong><span style="text-decoration: underline;">Advancing the Field</span></strong>&nbsp; &nbsp; &nbsp; <img src="https://www.closerlookatstemcells.org/wp-content/uploads/2019/03/fig2_basics_understanding-stemcells.tmb-medium.jpg" data-displaymode="Thumbnail" alt="Fig2_basics_understanding-stemcells" title="Fig2_basics_understanding-stemcells" style="float: right; margin-left: 10px;" />&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;<br />
The implications of the Gurdon/Yamanaka discovery have been wide-ranging and continue to help scientists understand cell biology and development. Through studying iPS cells derived from patients, researchers are gaining insights into the causes of a variety of diseases and their mechanisms in the body, and beginning to devise and develop potential new therapies:</p>
<ul>
<li><em>Precision Medicine</em>: iPS cells have shown promise as a tool in predicting how particular patients will respond to potential therapies. By developing iPS cells from patients or patient groups, researchers can test those cells with potential drugs to develop customized treatments to optimize individual patient outcomes.</li>
<li><em>Disease Modelling &amp; Drug Discovery</em>: Outside of the body, patient-generated iPS cells retain the same genetic and/or cellular defects they do in the patient. These cells can be analyzed in labs to uncover the underlying mechanisms of the disease, including the identification of new genetic and environmental causes. These &ldquo;diseases in a dish&rdquo; can also be used screen thousands of chemical compounds to discover new drugs that could potentially treat disease-affected cells.</li>
<li><em>Cell Therapies</em>: iPS cells could potentially be used to generate cell types that could be transplanted to replace those lost or damaged in organs or tissues due to injury or disease. Because they are the patient&rsquo;s own cells, they escape immune rejection that remains a serious concern for current organ transplants from donors. For example, experimental iPS cell therapies are being investigated that may one day replace neurons in <a href="https://www.closerlookatstemcells.org/2018/04/06/can-stem-cell-based-treatments-provide-a-durable-treatment-for-parkinsons-disease/">Parkinson&rsquo;s Disease</a> patient brains, different cell types of the eye for <a href="https://www.closerlookatstemcells.org/stem-cells-medicine/macular-degeneration/">degenerative eye conditions</a>, <a href="https://www.closerlookatstemcells.org/2019/02/08/enlisting-stem-cells-in-the-war-on-heart-disease/">heart cells for heart disease</a>, and more. </li>
</ul>
<p><strong><span style="text-decoration: underline;">Next Steps<br />
</span></strong>The process of moving a scientific discovery into an actual treatment available for patients takes many years, even decades, and there is currently no medical treatment that directly involves iPS cells, though many are being developed and some are in clinical trial.</p>
<p>In the meantime, scientists are looking to answer questions about how to standardize iPS cell lines to reduce variability of outcomes, determine how to make iPS cells uniform for any given use, and ensure their safety and efficacy before using the cells as potential treatments.</p>

Enlisting Stem Cells in the War on Heart Disease

<p>The heart works tirelessly for a whole lifetime, pumping fresh blood to the far reaches of the body, supplying oxygen and nutrients. When the heart itself is deprived of blood caused by a blocked artery, the affected tissue withers and scars and can no longer beat (see figure below). According to the World Health Organization, ischemic heart disease is the number one cause of death in men and women worldwide, far surpassing cancers and infectious diseases. </p>
<img src="https://www.closerlookatstemcells.org/wp-content/uploads/2019/02/adobestock_heartillustration497b23731dff6ddbb37cff0000940c19.png" data-displaymode="Original" alt="AdobeStock_HeartIllustration" title="AdobeStock_HeartIllustration" />
<p>Figure: When an artery is blocked by a plaque buildup or blood clot the heart is deprived of oxygen, leading to the death of heart muscle. This tissue will not regenerate on its own.<br />
<br />
February is heart disease awareness month, a time to take stock of how stem cells are being used to better understand and potentially treat heart disease. </p>
<p><strong><span style="text-decoration: underline;">Improving Cardiac Disease Treatment</span></strong></p>
<p>The heart is comprised primarily of cardiac muscle cells, called cardiomyocytes, which have very little, if any, inherent regenerative capabilities. Aside from a heart transplant there are currently no treatments which can restore heart function. Many researchers are exploring stem cell therapies as a way to supply the damaged area with functional cardiomyocytes that can replace the scarred tissue with healthy beating tissue.</p>
<p>Researchers can take skin cells, for example, from a patient and turn them into <a href="https://www.closerlookatstemcells.org/learn-about-stem-cells/types-of-stem-cells/#induced-pluripotent">induced pluripotent stem cells</a> (iPSCs). iPSCs can then be directed to become any cell in the body, including cardiomyocytes, by exposing them to specific signals or chemicals. As current treatments only manage disease symptoms, restoring function with cell therapy would be a new modality for treating heart disease.</p>
<p><strong><span style="text-decoration: underline;">Beating Heart Cells in the Lab</span></strong></p>
<p>Stem cell derived-cardiomyocytes beat in the lab, just like they do in the heart. Getting these cardiomyocytes to mature properly and meet the energy demands that the heart experiences after birth, however, has proven very difficult. Scientists are working to generate cardiomyocytes in the lab that more closely mimic cells in the adult heart.</p>
<p>A <a href="https://www.sciencedaily.com/releases/2018/04/180404133526.htm">research group from Columbia University</a> found that by recreating the cardiomyocytes&rsquo; natural environment, using stimuli to contract the cells and send them electrical pulses, they were able to coax mature stem cells into a model of adult-like cardiac muscle. Researchers can now use these cells that more closely mimic the cells in our hearts to model disease and test new drugs. In the future, similar techniques may yield cells that can be directly transplanted into patients. </p>
<p><strong><span style="text-decoration: underline;">Remuscularizing the Heart</span></strong></p>
<p>A <a href="https://www.sciencedaily.com/releases/2018/07/180702154723.htm">group at the University of Washington</a> recently demonstrated the potential of cardiomyocytes grown from stem cells to replace diseased heart muscle. These cardiomyocytes were injected into the damaged areas of the heart in a primate model of heart disease. After injection, cells were able to attach to the scar tissue, grow in number, and extend a new layer of healthy heart muscle. Importantly, these stem cell-derived cardiomyocytes led to an increase in heart muscle strength, with contractions pumping larger amounts of blood around the body.</p>
<p>There is more fine-tuning required, but this research demonstrates a proof-of-principle approach and brings us one step closer to understanding how to repair human hearts.</p>
<p><strong><span style="text-decoration: underline;">Patching Broken Hearts</span></strong></p>
<p>A limitation of the above approach is that when cells are injected into the heart, they leak away with every heartbeat. This therapy is therefore inefficient due to the low retention of cells in the diseased area. To overcome this, <a href="https://www.bsgct.org/stem-cells-to-mend-a-wounded-heart/">researchers and doctors in Paris</a> engineered a gel matrix, or patch, into which they grew the cardiac progenitor cells. They then inserted the gel beneath the top layer of the diseased region of the heart to promote targeted growth of the cardiomyocytes into new muscle. </p>
<p>The number of patients treated was too small to conclusively determine whether the treatment was effective, however it is important to note that one year later none of the treated patients had detectable tumors or presented with arrythmia (irregular heartbeats), a current clinical risk. &nbsp;This first trial using the patch demonstrates that cardiac progenitors can be delivered safely with low risk of adverse effects. More research will be required to determine whether this approach will successfully treat heart disease.</p>
<p><strong><span style="text-decoration: underline;">What Does the Future Hold?</span></strong></p>
<p>The field of cardiac regeneration is fast evolving, as scientists continue to harness the power of stem cells to generate healthy heart muscle and fine-tune their methods of making cardiac cells. However, challenges remain:</p>
<ul>
<li>Engineering cardiomyocytes has not yet been perfected;</li>
<li>Transplanted cardiomyocytes still run the risk of generating arrhythmic heart beats;</li>
<li>Significant benefits have not yet been recorded in human trials. </li>
</ul>
<p>Patients should be cautious of<a href="https://www.closerlookatstemcells.org/stem-cells-medicine/nine-things-to-know-about-stem-cell-treatments/"> clinics offering unproven stem cell interventions</a> targeted at cardiac disease; the treatments have not been proven safe or effective.</p>
<p>Scientists are advancing in their ability to make functionally useful cardiomyocytes and demonstrating functional benefits in animal models of heart disease. With continued progress, these pre-clinical advances will be translated into successful treatments that will make strides in the fight against heart disease. For more information see this <a href="https://www.closerlookatstemcells.org/stem-cells-medicine/heart-disease/">overview of heart disease and current therapies</a>.</p>
<p><em>Special thanks to Edie Crosse, PhD student at the MRC Centre for Regenerative Medicine, University of Edinburgh, for this guest blog post.</em></p>
<p>&nbsp;</p>

Single Cell Sequencing: Unwinding Embryonic Development One Cell at a Time

<p>At one point, we were all just one single cell: a fertilized zygote formed when a sperm and egg fused together. That one cell gave rise to all of the roughly 37 trillion specialized cells that make up each of our bodies today. All the cells from our heads to our toes, <em>every single one of them,</em> can be traced back to one single cell. </p>
<p>The mystery of how embryonic development choreographs the formation of specialized tissues and organs from one original cell has captivated, and baffled, developmental biologists for centuries. How does one cell divide and specialize into different cell types? How do cells know when, where, and what kind of cell to become (e.g. a brain cell versus a blood cell)? Recently named the 2018 <em>Science Magazine</em> &ldquo;<a href="http://vis.sciencemag.org/breakthrough2018/finalists/#cell-development">Breakthrough of the Year</a>,&rdquo; single cell sequencing allows scientists to retrace the steps that cells took during development, one cell at a time. </p>
<p><strong>A family tree of cells</strong></p>
<p>Every cell is related to all of the others within a living organism. Imagine drawing a family tree where an initial fertilized cell is at the apex and every subsequent cell division leads to successive branching. That single cell would become two, then four, then eight, and so on. After many, many cell divisions the family tree would result in 37 trillion progeny, all with one common ancestor cell at the very top. Now <em>that&rsquo;s</em> a family tree!</p>
<p>By developing a detailed family tree outlining the steps that cells undertake during development, scientists hope to piece together a blueprint of how different cell types are made in organisms and how some diseases progress. It could also help them mimic the process with stem cells in the lab to make replacement tissues and organs for those damaged by injury or disease.</p>
<p><strong>Going back in time</strong></p>
<p>The combination of three cutting-edge technologies, single cell sequencing, <a href="https://www.closerlookatstemcells.org/2017/04/17/a-crispr-method-for-gene-editing-a-biomedical-breakthrough-from-a-germ/">CRISPR gene editing</a>, and powerful computer algorithms, has enabled scientists to retrace the cells of entire organisms back to their early embryonic stages, in order to understand how they form. The work is not yet being done in humans, but several pioneering studies have been carried out in smaller organisms. </p>
<p>Scientists are able to track cells when they are at the embryonic stage by branding them with different DNA barcodes that can be read (sequenced) at later times. After an organism develops, the DNA or RNA in individual single cells can be sequenced, thus the term &lsquo;single cell sequencing.&rsquo; The barcodes identify which cells in the early embryo gave rise to which cells in the adult, retracing the history of individual cells.&nbsp;</p>
<p><strong>Tracing cellular development</strong></p>
<p>Scientists have made great progress in retracing cell lineages in small, simple organisms. In <a href="https://phys.org/news/2018-03-scartrace-multicellular-embryonic-progenitors.html">zebrafish</a>, as many as 92,000 cells from <a href="https://news.harvard.edu/gazette/story/2018/04/path-to-building-an-entire-organism-from-single-cell-is-revealed/">one fish</a> were retraced back to their progenitors in the early embryo. After retracing the development of fish, worms, frogs, and salamanders, in August, 2018, scientists reported using single cell sequencing to study the <a href="https://wyss.harvard.edu/recording-every-cells-history-in-real-time-with-evolving-genetic-barcodes/">development of a whole mouse</a>. Together, studies over the last year have revealed:</p>
<ul>
<li>some organ systems appeared to be established from small numbers of founder cells very early in development (e.g. the blood system);</li>
<li>seemingly similar cell types can have different developmental histories;</li>
<li>the front-back axis of the brain may develop before the left-right axis; </li>
<li>&middot;novel roles for genes in the development of different cell types. </li>
</ul>
<p>In addition to unraveling fascinating mysteries of embryonic development, this technology may provide key insights into how diseases develop, and how cells might be regenerated for repair.</p>
<p><strong>Applying this technology to help people</strong></p>
<p>Single cell sequencing is fundamentally revolutionizing how researchers study and understand embryonic development. By tracking organs cell by cell over time, scientists may better understand how diseases such as Alzheimer&rsquo;s, Parkinson&rsquo;s, Amyotrophic Lateral Sclerosis (ALS), diabetes, or even cancers originate and develop. These insights may lead researchers to find ways to repair tissues or organs, replicate processes in the lab to make cell types to help patients, or find new strategies to prevent or fight devastating diseases. We are just learning about the many ways this technology can be applied to research to advance human health.</p>