Scientists Discover Bone-a fide Human Skeletal Stem Cell

<p>If you&rsquo;ve ever broken a bone, you are not alone. Statistics show that, over a lifetime, the average person experiences 2 bone fractures. For those with osteoporosis, that figure escalates, on average, to one bone fracture every 3 seconds, or nearly nine million fractures a year. Bone fractures, bone pain, and deformities that result from skeletal trauma and disease cause significant personal and economic burdens.</p>
<p>&nbsp;Recently, scientists have discovered a new cell type, human skeletal stem cells, that are providing insights into human skeletal development. These cells, which give rise to both bone and cartilage, may help researchers design potential therapeutic approaches to treat skeletal injuries and diseases.</p>
<p><strong>What is the skeletal system made of?</strong></p>
<p>The human skeleton is comprised of many different cell types, including bone, cartilage, and stroma, a type of supportive tissue. While it might seem rather inert, your bone is a living tissue that is always undergoing self-renewal&mdash;old cells are constantly being replaced by newer cells. In young people, the rate of bone turnover yields a net gain in bone mass. With age, bone growth slows and bone mass is gradually lost, which can lead to fragile bones that are more likely to fracture (see figure). Bone breaks can heal on their own, however they don&rsquo;t always heal perfectly. Cartilage, on the other hand, exhibits little, if any, regenerative properties. Until the recent discovery, the stem cell that gives rise to these skeletal tissues had eluded scientists.</p>
<p>
<br />
<img src="https://www.closerlookatstemcells.org/wp-content/uploads/2018/12/healthy-bone-and-broken-bone-with-osteoporosis982c23731dff6ddbb37cff0000940c19.tmb-small-2.png" data-displaymode="Thumbnail" alt="Healthy bone and broken bone with osteoporosis" title="Healthy bone and broken bone with osteoporosis" /><br />
Illustration of normal bone (left) as compared to aged or diseased bone (right) that has reduced mass and is more susceptible to fracture. </p>
<p><strong>Is there a human skeletal stem cell?</strong></p>
<p>A research team from Stanford University, USA set out to <a href="https://www.the-scientist.com/news-opinion/human-skeletal-stem-cell-found-64830">find and identify human skeletal stem cells</a> to better understand their growth and repair. They found cells in the growth plate of fetal human femur bones that could <a href="https://www.closerlookatstemcells.org/patient-resources/resources-from-isscr/stem-cell-glossary/#selfrenewal">self-renew</a> and give rise to bone, cartilage, and stroma, which defines them as the human skeletal stem cell (hSSC). Human SSCs could be isolated from both fetal and adult bone, and upon comparison appear to become more specialized with age. Researchers found that stem cells isolated from different tissues had different inherent properties, with stem cells isolated from fetal tissue more likely to form cartilage than those derived from adult bone, similar to normal development.</p>
<p>To determine whether hSSCs respond to injury, researchers examined their behavior in skeletal samples from patients undergoing bone grafts and found that hSSCs do expand in response to fracture, indicating regenerative behavior. Scientists also found that hSSCs can give rise to supportive stromal tissue which can fulfill a critical role of the bone marrow – supporting blood stem cells. The ability to grow blood cells in the lab has so far eluded scientists, but better mimicking their natural environment could improve these efforts. These discoveries have great potential for regenerating tissue to repair the human skeleton and all that entails. </p>
<p><strong>How did humans grow so tall?</strong></p>
<p>Identifying the hSSC also allowed researchers to learn about human-specific genes that regulate bone growth. By comparing human and mouse skeletal stem cells, scientists have identified genetic differences that may account for changes in size and biomechanical properties. While the majority of expressed genes are common to both human and mouse SSCs, several human-specific genes, when expressed in mouse skeletal stem cells, led to increased bone growth. It therefore appears that these genes regulate skeletal size at the stem cell level. Scientists may eventually find ways to modify these genes to promote stem cell self-renewal or promote the formation of bone or cartilage.</p>
<p><strong>Correcting an earlier misconception</strong></p>
<p>Discovery of the hSSC, a &ldquo;bone-a fide&rdquo; skeletal stem cell, dispels earlier assumptions that <a href="https://www.closerlookatstemcells.org/learn-about-stem-cells/types-of-stem-cells/#mesenchymal">mesenchymal stem cells</a> (MSCs) were the stem cell population in the bone. MSCs are a controversial and poorly characterized heterogenous population of multiple types of cells, which includes stem cells. hSSCs provide potential for therapeutic use, however more testing and replication is needed before they can be considered for clinical use.</p>
<p><strong>Potential for healing and repair</strong></p>
<p>We know that our ability to repair and regenerate bones and joints diminishes with age, and now we can better understand the injury and aging processes by studying the cells that generate these tissues in humans. With further study, we hope to gain insight into how to better diagnose skeletal diseases, and one day identify treatments that could activate stem cells in the injured or diseased body, produce new bone or cartilage in the lab for replacement cell therapy, and develop personalized therapies.</p>

The Ubiquitous Stem Cell Sales Pitch

<p><strong>Do you suffer from [insert disease/condition/injury here]? Attend our seminar to learn how stem cell therapy is helping people just like you!</strong></p>
<p>These advertisements increasingly appear on the internet or in multi-page print ads, and they&rsquo;re now in television and radio spots too. These seminars are the latest attempts by rogue stem cell clinics to promote their products, which are untested and have little, if any, rigorous scientific support. </p>
<p>To understand how clinics present and promote their stem cell-based products, we attended a seminar held at a local hotel in the U.S. Midwest. Following are some of the tactics we observed.</p>
<p><strong>The Clinic Pitch</strong></p>
<p>We quickly saw that the seminars are designed to appeal to those struggling with a chronic health condition with promotional brochures and emotional patient testimonials playing on large screen televisions. The opening presentation by a paid spokesman is designed to convey that they&rsquo;re selling a new approach; words like &ldquo;cutting-edge,&rdquo; &ldquo;revolutionary,&rdquo; &ldquo;scientifically-proven,&rdquo; and &ldquo;regenerative medicine&rdquo; are liberally used throughout the presentation. Those looking for a solution to a chronic health issue can easily get the false sense that these treatments are special, and that they will work. </p>
<p>The seminar we attended was meant to address joint pain from osteoarthritis or orthopedic issues, however the message was that stem cells have broader, nearly unlimited therapeutic potential. In numerous video testimonials, middle-aged men and women mentioned how, following a stem cell injection for joint pain, their pain was lessened, their skin &ldquo;glowed,&rdquo; and they had more energy. Several patients had multiple ailments and mentioned improvement in diabetes and Chronic Obstructive Pulmonary Disease (COPD) symptoms. Ultimately, attendees are led to believe that stem cells have magical qualities and can treat nearly anything if given the time and enough injections. The clinic doesn&rsquo;t let facts get in the way of a good story or closing a sale.</p>
<p><strong>Moving to Close the Sale</strong></p>
<p>The presentation generalized and distorted the current state of stem cell science, overpromising on what might work to treat disease. There were no medical professionals present, and the doctor listed on the clinics&rsquo; business cards was a chiropractor &mdash; not a specialist in the areas promoted such as diabetes and COPD. Afterward, rather than fielding questions from the audience, a handout was provided as a learning tool to help reinforce the misguided &lsquo;facts&rsquo; presented by the speaker. To close the sale, attendees were offered a one-time opportunity, only available that day, for a consultation with a chiropractor. The fee, a discounted rate of $79 USD, would not include the $3715 required to receive one stem cell &ldquo;treatment.&rdquo; Hurry, appointments are filling up fast!</p>
<p>At best, the scientific and medical content of the seminar demonstrated the naiveite of the clinic and its medical team about stem cells and how they work; at worst, it deliberately misled attendees.</p>
<p>One last emotional appeal was made in a split-screen video of two older men, one who had received a &ldquo;therapy&rdquo; and one who did not. The first man was happy and leading an active life, in contrast with the man who didn&rsquo;t receive a stem cell product, who lived an unhappy, sedentary life and died. The video closed with the words &ldquo;it&rsquo;s time to decide.&rdquo; </p>
<p><strong>How to Decide?</strong></p>
<p>For those in pain and/or suffering from life-altering disease or injury, there is a strong desire to believe that a cure is imminent, and to look to medical science to provide relief. Several of the seminar attendees failed to find that relief through standard clinical care approaches &ndash; the diagnosis, hours of physical therapy, medication or pain management procedures, and surgery so they are looking for something different.</p>
<p>Stem cell research is making very real advances, but for many diseases and conditions, there are currently no effective treatments. Rogue stem cell clinics, peddling unproven, untested, and often unknown &lsquo;treatments,&rsquo; do a disservice to medical science and distort the public&rsquo;s perception of stem cell research and its potential for real biomedical breakthroughs. They also exploit the hope and motivation of the very patients they claim they want to help.</p>
<p>To learn more about the potential of stem cell treatments, check out <a href="http://www.closerlookatstemcells.org/stem-cells-and-medicine/stem-cell-treatments-what-to-ask">Stem Cell Treatments: What to Ask</a>.</p>

Stem Cells and Aging – What Happens When Our Stem Cells Get Old and Tired?

<p>Aging is an inevitable, unnerving process that confronts us all. Eventually our muscles and immune systems will weaken, our hair will thin, and our minds won&rsquo;t be as sharp as they once were. But what is the biology that underlies this process? And what if advances in the field of regenerative medicine could counteract this decline and alleviate the symptoms of old age?</p>
<p><strong>Do Our Stem Cells Age as We Do?</strong></p>
<p>Consider the body not as a single entity but as a dynamic multitude of cells growing, changing, dying, and being born. These cells make up and replenish the bodies&rsquo; tissues and organs, acting in concert and communicating in fascinating ways to keep the body in good working order. In many tissues, adult stem cells are at the root of this process, tasked with supplying cells to maintain normal tissue function and facilitating regeneration in response to injury. It is logical then to assume that, as our bodies grow older and our organs and faculties begin to degenerate, our stem cells must be failing us. </p>
<p>In fact, much research has gone into uncovering what happens to our stem cells as they age. For example, hematopoietic stem cells, which produce all the cells of the blood and immune system, actually increase in number in aging adults. Unfortunately, the expansion in cell numbers is to compensate for their overall loss in functionality. Ultimately, fewer white blood cells are produced, which contributes to a deficient immune system and diminished resistance to disease and infections in the elderly. </p>
<p><strong>What About Stem Cells in Our Brains?</strong></p>
<p>One fascinating avenue of research focuses on what happens to stem cells in the brain as we age. Until the 1960s it was believed that we are born with our lifetime&rsquo;s supply of brain cells. This dogma was broken by the discovery of neural stem cells (NSCs), which reside in certain regions of the brain. &nbsp;Now we know that NSCs do have the ability to produce glia and some types of neurons in certain conditions. As NSCs age, however, their ability to regenerate lost or damaged brain cells decreases and they have a significant reduction in the number of neurons they can generate.</p>
<p>Fortunately, the advent of technology to identify and isolate these NSCs means we can study how they change as they age and, armed with this knowledge, begin to innovate ways to halt or reverse the aging process. Recently published <a href="https://www.sciencedaily.com/releases/2018/03/180315141229.htm">research from a group at Stanford University</a> provides fascinating new insights. Using a mouse model, the team investigated the differences in NSCs between young and old mice and found that as NSCs age they do a poor job of clearing away broken proteins that can interfere with the normal functions of the cells. Aged NSCs have an increased accumulation of protein aggregates, or clumps of broken proteins. This is striking as a number of age-related neurodegenerative diseases, such as Alzheimer&rsquo;s and Parkinson&rsquo;s disease, are linked to a build-up of proteins that can clog up brain cells and cause them to malfunction or die.</p>
<p>The researchers discovered that the inability of aged NSCs to clear broken proteins impairs their activation and production of new neurons. In the study they found that artificially stimulating the protein clearing system in aged NSCs gave them a new lease on life, restoring their ability to generate neurons, and increasing the number of active NSCs in elderly mouse brains. This type of fundamental research enhances our understanding of the biology of aging and provides the scientific underpinning for potential new treatments that could improve people&rsquo;s health into old age. </p>
<p><strong>Can We Treat Aging?</strong></p>
<p>Although most research is far from the clinic, new drugs are being developed with the potential to treat degenerative age-related diseases, some by potentially promoting stem cell regeneration. It will take time and controlled clinical trials to determine the safety and efficacy of these treatments. In the meantime, some companies are harvesting and freezing young stem cells, with the hope that the cells will be useful in the future and will be able to delay or reverse aging. While this may sound appealing, at the moment, &ldquo;[t]here is no way to extend anybody&rsquo;s life with stem cells,&rdquo; as former ISSCR President Sean Morrison <a href="https://www.bloomberg.com/news/articles/2018-08-27/companies-offer-employees-hope-with-stem-cell-storage-benefits">said in a recent interview</a>, and consumers should be wary until further studies have been done.</p>
<p>The study of stem cell aging is a field of research at the cutting edge of biomedical innovation. With incremental progress, research groups around the world are uncovering the biology of why and how stem cell function declines with age. The hope is that one day this fundamental research will be translated into treatments that enhance the health and quality of life for future generations. </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>

Gene Therapy: Treating the Cause, Not the Symptom

<p>Gene therapy, CRISPR, and gene editing are all terms that are beginning to appear more frequently in headlines, and the concept of manipulating DNA inside cells &ndash; once found only in science fiction &ndash; is now reality. In fact, gene editing is routinely done in labs around the world, with potentially transformative applications for medicine. In this post, we discuss what gene therapy is, what is new and exciting in the field, and why the technology could change the way we treat certain diseases.</p>
<p><strong>What is gene therapy?</strong></p>
<p>Gene therapy can be defined as making changes to the DNA inside of cells to treat disease. Each person is made up of trillions of cells, each with DNA that encodes about 25,000 genes. Sometimes, one or more of these genes is broken (mutated), which can lead to serious debilitating and devastating disease. Gene therapy can be used to either add a new, healthy copy of the gene, or repair the existing broken gene so it&rsquo;s healthy again (called &lsquo;gene editing,&rsquo; a type of gene therapy).&nbsp;ISSCR researchers describe some of their work in this area <a href="https://www.youtube.com/watch?v=u14vP-_-nso&amp;feature=youtu.be" target="_blank">here</a>.</p>
<p><strong>How is gene therapy different than current treatments? </strong></p>
<p>When researchers completed sequencing the DNA of the human genome in 2003, part of the hope was to identify genes that cause disease when they malfunction, so that one day scientists could potentially fix the underlying genetic causes of disease, rather than just treat its symptoms as many conventional therapies do. They envisioned a transformative field of medicine: gene therapy. </p>
<p><strong>How does gene therapy work?</strong></p>
<p>Whether using gene therapy to fix a broken gene or add a new healthy copy of that gene, new DNA must be inserted into cells. A common way that scientists add healthy DNA to cells is by using viruses &mdash; nature&rsquo;s own DNA syringe. Viruses have evolved highly effective ways to inject their DNA (or RNA) into host cells; harnessing that same method for good, scientists can replace the harmful DNA found inside some viruses with healthy DNA that can help patients. When these modified viruses encounter a cell, rather than injecting them with harmful virus DNA, the virus inserts healthy DNA to repair or replace the broken gene. Genes can either be repaired inside the body by injecting the virus directly into the patient, or the cells can be removed first, repaired in a lab outside the body, and then transplanted back into the patient.</p>
<p><strong>What technologies are used to find and repair genes?</strong></p>
<p>Finding a broken or damaged gene can be a challenge. There are roughly 25,000 genes in each cell, but each gene can be made up of thousands of building blocks called &lsquo;base pairs&rsquo;, adding up to a total of 3 billion base pairs in each cell. How do scientists target one of 3 billion base pairs to fix the mutated gene? </p>
<p>Early pioneering technologies use designer proteins that act like DNA-cutting scissors capable of finding specific base pairs in the human genome and snipping DNA inside of cells, causing the gene to be repaired with healthy DNA. Over time, however, these proteins were found to be difficult and time-consuming to design, expensive, inefficient, and challenging to modify for new genes. In just the last five years, a new molecular scissor-based system, <a href="https://www.closerlookatstemcells.org/blog/blog/2017/04/17/A-CRISPR-Method-For-Gene-Editing-A-Biomedical-Breakthrough-From-a-Germ-" target="_blank">CRISPR</a>, has become the breakthrough technology that has catapulted the efficiency and simplicity of gene editing to new levels, allowing scientists the flexibility to edit almost any part of the human genome with pin-point accuracy and ease, and at a fraction of the price. The CRISPR era has sparked real excitement among scientists worldwide.</p>
<p><strong>Diseases actively being investigated as candidates for gene therapy</strong></p>
<p>The first wave of gene therapy research is aimed at diseases that have clearly defined mutations within a single gene. These diseases include <a href="https://www.closerlookatstemcells.org/blog/blog/2017/04/17/An-Exciting-Strategy-for-Treating-Sickle-Cell-Disease-with-Stem-Cells" target="_blank">blood disorders</a>, cystic fibrosis, <a href="https://www.closerlookatstemcells.org/blog/blog/2018/02/13/Novel-Stem-Cell-Therapy-Grows-New-Skin" target="_blank">skin disorders</a>, muscular dystrophy, Hunter syndrome, and some degenerative eye conditions, among others. Gene editing can also help treat cancer by modifying the patient&rsquo;s own immune system to target and kill cancer cells, known as <a href="https://www.closerlookatstemcells.org/blog/blog/2017/10/27/CRISPR-CAR-T-and-Cancer" target="_blank">CAR-T therapy</a>.</p>
<p>Importantly, all gene therapies currently in clinical trials do not edit DNA in sperm or eggs, and therefore the changes made to the DNA will <a href="https://www.closerlookatstemcells.org/blog/blog/2017/04/17/What-to-Consider-Human-Genome-Germline-Modification" target="_blank">not be passed on to future generations</a>. </p>
<p><strong>Future possibilities</strong></p>
<p>Gene therapy is a promising and exciting therapeutic approach, and may eventually be useful in treating many diseases, particularly when combined with stem cell technologies. Before it is routinely used in the clinic, however, important safety and health concerns need to be addressed. The most pressing concern is the accuracy and specificity of gene modifications; any unintended changes to the DNA could potentially introduce health risks. However, researchers are now aware of these concerns and are working hard to understand the issues involved and minimize the risk. </p>
As they are developed, new and evolving technologies are granting scientists the ability to fix the once-inaccessible causes of many devastating genetic diseases &ndash; the genes themselves. With further rigorous testing and study, transformative gene editing therapies could potentially be on the horizon for several diseases for which there are currently no cures.

Stem Cell Scientists and The Public: Personal Reflections

<p>A <a href="http://www.closerlookatstemcells.org/blog/blog/2018/07/10/Learning-about-Stem-Cells-Down-Under-">recent public forum</a> in Melbourne, Australia, &ldquo;<a href="https://www.youtube.com/watch?v=zkzHvtZgWc0&amp;feature=youtu.be" target="_blank">Stem Cell Research &ndash; Now and in the Future</a>,&rdquo; allowed scientists and experts to share with the public the potential of this rapidly advancing research. There are many ways in which scientists, including our members, are using science outside of the laboratory for the public interest. In this blog post, three Australian stem cell scientists who attended the session describe their personal reflections on public engagement.</p>
<p><strong><em>Recognizing the Public&rsquo;s Contributions to Science</em></strong></p>
<p><em>By Freya Bruveris, PhD, </em><em>Murdoch Children&rsquo;s Research Institute</em></p>
<p>At the public forum, I had the opportunity to talk with an amazing woman I&rsquo;ll call Sarah. Meeting Sarah reminded me of the significant contribution the public can make in supporting scientific discovery in general, and with my own research specifically. For years, Sarah donated her eggs for <em>in vitro</em> fertilization (IVF). She knew that her fertilized eggs may have both helped couples with infertility and may also have been donated to science with the potential to help thousands more.&nbsp;</p>
<p>Cell and tissue donation is critical for the advancement of science and my research. Because of donated embryos, scientists were able to derive the first human embryonic stem (hES) cells in the laboratory in 1998, which today allow scientists to study many aspects of human biology and disease. Every day in the laboratory I am working to derive blood cells from hES cells in the hopes of treating individuals with blood disorders. The origin of the hES cells that I use for all of my experiments is intrinsically linked to donated embryos. This conversation with Sarah was very special as donations like hers have made my research possible. Without the public, neither my stem cell research nor that of thousands of scientists worldwide would be possible. With this in mind, I am indebted to repaying these extraordinary gifts every day in the laboratory through my work.<br />
<em>__________________</em></p>
<p><strong><em>Outreach to Bring About Change</em></strong></p>
<p><em>By Jennifer Hollands, PhD, <em>The Florey Institute of Neuroscience and Mental Health</em></em></p>
<p>I often get asked by my friends and family &lsquo;when are you going to cure my ailments with stem cells?&rsquo; Given that the public is bombarded by advertisements from private stem cell clinics claiming that stem cells can easily and effectively cure most any disease, it&rsquo;s a fair question. Many available treatments, however, have not been rigorously tested or shown to be safe or effective. As a scientist I feel it is my responsibility to ensure that consumers are protected by evidence-based policies. Towards this end, I recently spoke to the public and lobbied the government for greater consumer protection.</p>
<p>Until recently in Australia, medical doctors could isolate a patient&rsquo;s own cells, &lsquo;minimally manipulate&rsquo; them, and re-administer them to the same patient without regulatory oversight. The majority of these stem cell therapies lacked scientific support, have not been rigorously tested in clinical trials, or proven to work as advertised. In fact, they can cause serious harm to patients. Scientific organizations including Stem Cells Australia and the ISSCR raised these issues before the Australian regulatory body, urging them to hold an open public hearing on the regulation of these stem cell therapies. At the hearing I joined other stem cell scientists in raising awareness of the risks of unproven stem cell interventions. In response, new regulations will go into effect this year that scrutinize stem cell clinics, protect consumers, and will hopefully reduce the number of predatory stem cell clinics. Having contributed to the introduction of tougher regulations, I&rsquo;ve seen first-hand how critical it is for scientists like me to use their expertise and engage on behalf of the public. <br />
<em>____________________</em></p>
<p><strong><em>Helping Loved Ones (and the Public) Learn about Science</em></strong></p>
<p><em>By Ana Rita Leitoguinho, PhD Candidate, <em>Murdoch Children&rsquo;s Research Institute</em></em></p>
<p>As the only scientist in my family, it is up to me to translate scientific jargon into everyday language. As soon as I mention &ldquo;stem cells&rdquo; I see their eyes light up and I know they are impressed by the research I do, thinking of me as some sort of wizard. After all, scientists do wear distinctive long coats and talk in a peculiar language. It is vital for scientists to break down this language barrier.&nbsp;</p>
<p>By understanding the differences between healthy and damaged tissues, scientists can work to develop therapies to repair them. This process of translating research to an effective treatment is a long and laborious one. As a concerned daughter, I explain this process to my mum so she understands that while progress is slow, it is advancing. She needs to be able to distinguish science from non-science when she sees news on tv or social media, and to understand that stem cells can&rsquo;t yet be used to cure her breast cancer. Because she understands this she can retain hope without falling prey to spurious therapies.&nbsp;</p>
<p>It is important for scientists to engage the public to create awareness, capture their imagination, ensure they are informed, and gain their support to fund research. Correspondingly, the public needs scientists to study diseases, develop treatments, and explain the progress. As in every relationship, communication is key. Scientists need to be able to explain their science because, at the end of the day, we are not wizards, we are just people, and we cannot do this work alone. <br />
<em>____________________</em></p>
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Learning about Stem Cells Down Under

<p>Stem cell research was recently brought out of the laboratory and into the public discourse in an open public forum held in conjunction with the 16<sup>th</sup> Annual Meeting of the International Society for Stem Cell Research (ISSCR) in Melbourne, Australia, and was proudly sponsored by the National Stem Cell Foundation of Australia.</p>
<p>The public forum, &ldquo;<a href="http://www.isscr.org/docs/default-source/2018-melbourne-ann-mtng/stem_cells_public_forum_2018.pdf?sfvrsn=2">Stem Cell Research &ndash; Now and in the Future</a>,&rdquo; was held at Deakin&rsquo;s Edge in Federation Square, and featured stem cell scientists sharing their research and answering questions from a crowd of people curious about stem cell research. Before the panel discussion began, early-career researchers were on-hand to explain their science, and a <em>Stem Cell Stories</em> photography exhibit showed how stem cells can look under the microscope, giving an appreciation for how these cells can be studied.&nbsp;</p>
<p><em>A spotlight on Australian stem cell research <br />
</em>Australia has a long history and record of achievement in stem cell science, and the panel of leading Australian researchers explained how they use stem cells to understand normal and abnormal biological processes in the blood, skin, heart, eye, and kidney.</p>
<p>&middot;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Professor Susie Nilsson from the Australian Commonwealth Scientific and Industrial Research Organisation opened the session by discussing her work to improve bone marrow transplantation, the oldest clinically approved stem cell treatment, which has its roots in Australian research. Strikingly, transplanted blood stem cells can cure patients of a variety of blood cancers or anemias. Dr. Nilsson has identified a small molecule that both improves the ability to collect these stem cells for transplantation and helps target leukemic stem cells for destruction, which she is bringing to phase I clinical trial to try to improve bone marrow transplantation for patients worldwide.&nbsp;</p>
<p>&middot;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Associate Professor James Chong from the University of Sydney is researching how stem cells can be used to treat heart disease. In the lab, he can use stem cells to make billions of heart muscle cells, which you can see beating together in a dish. He is currently working out how he can deliver these cells to patients to repair cardiac muscle after a heart attack.&nbsp;</p>
<p>&middot;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Dr. Michael O&rsquo;Connor of Western Sydney University is using stem cells to study the lens and the process by which it forms cataracts. Since the location of the lens within the eye makes it inaccessible, he has figured out how to use stem cells to make micro-lenses that can focus light and develop cataracts. He is hoping to use these stem cell-derived lenses to identify drugs that can delay cataract formation in adults or be transplanted into the eyes of children who have already developed cataracts.&nbsp;</p>
<p>&middot;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Associate Professor Pritinder Kaur of Curtin University was the first to isolate skin stem cells from human skin and demonstrate their ability to regenerate large areas of epidermal tissue. &nbsp;She discussed how she is trying to improve upon this stunning therapy, which can replace skin covering the surface of most of a human by improving the regeneration of other key cell types in the dermis that are also required for critical functions.&nbsp;</p>
<p>&middot;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Closing the series of presentations was the chair of the Program Committee for the ISSCR meeting, Professor Melissa Little from Murdoch Children&rsquo;s Research Institute talking about her work on the kidney. Unfortunately, only one in four patients with kidney disease is able to receive a transplant. She has built a mini-kidney in a dish that can be used to identify drugs to improve kidney disease, and hopefully one day can build a kidney large enough that could be transplanted into a human patient.&nbsp;</p>
<p><em>Promising Area of Medical Research<br />
</em>The audience had a number of questions about the stem cell field, and the potential of this science to treat and cure disease. Questions focused on how technology might speed up stem cell research, the future of stem cells in the clinic, and the status of stem cells in clinical trials (<a href="https://youtu.be/zkzHvtZgWc0">view the complete forum</a> including answers to all of these questions and visit<a href="http://www.closerlookatstemcells.org/"> A Closer Look at Stem Cells</a> to learn more).&nbsp;</p>
<p>The panelists described their views of a changing future of amazing, but potentially disruptive, technology and the need to proceed with research in a careful and ethical manner. Together, gene therapy and stem cell research have the ability to make new cells that can do new things, and the speakers mentioned the next generation of therapeutics that are currently being developed. Moderator Megan Munsie, winner of the 2018 ISSCR Public Service Award, discussed the promise of treatments and the need for stem cell therapies to be tested through clinical trials to ensure that cell products delivered to patients have scientific justification and are proven to be safe. Panelists stressed the need for the field to progress safely and integrate what is learned from experience as the science develops.&nbsp;</p>
<p><em>Important Outreach<br />
</em>Engaging with the community and policy makers is key for scientists. When we explain what we do and how our work is making a difference in improving public health, we can generate support for science and drive innovation forward. Dr. Little cautioned that &ldquo;science is a slow process,&rdquo; and public patience is required so that researchers and clinicians can ensure new stem cell therapies are rigorously tested and shown to be safe and effective before they are made available in mainstream medical practice.&nbsp;</p>
<p>By developing an open dialogue between stem cell researchers and the public, together we hope to usher in a new and exciting era of medicine in which some diseases currently termed &lsquo;untreatable&rsquo; will become treatable in the near future.&nbsp;</p>
<p><em>Guest post by Stem Cells Australia members Freya Bruveris and Ana Rita Leitoguinho from Murdoch Children&rsquo;s Research Institute, and Jennifer Hollands from The Florey Institute of Neuroscience and Mental Health. Be sure to check back next month for a future post by these guest authors.</em></p>

Stem Cells as Anti-Cancer Vaccines?

<p>Vaccines are routinely used to increase immunity against a variety of infectious diseases, such as influenza, measles, and chicken pox, to name a few. Rather than vaccinating against viral infectious diseases, however, imagine a vaccine that could prevent cancer. </p>
<p>Researchers have long been interested in developing a vaccine that can help the body&rsquo;s immune system and fight abnormal, cancerous cells. Certain immune cells, called T cells, regularly scan the surface of every cell in the body and check if they appear normal. Imagine a cell is wearing a printed Hawaiian shirt: the pattern has several parts, such as palm trees and a beach scene, and it repeats. T cells check each cell to be sure that there are no irregularities to the pattern &mdash; i.e. changes to color, size, number of palm fronds, etc.&nbsp; </p>
<p>New patterns on a cell (such as a ketchup stain) may indicate that the cell is either infected by a virus or bacteria, or damaged in way that could cause cancer.&nbsp; When T cells identify damaged, aberrant cells they kill the cells so that they can&rsquo;t grow or divide. Occasionally, however, T cells may not detect a problematic change, and the abnormal cell grows unrestrained, potentially into a tumor. Scientists are working on creating vaccines that could be used to help T cells identify cancerous cells, so they can be eradicated, preventing tumor formation.</p>
<p><strong>Using vaccines to activate the immune system to fight cancer</strong></p>
<p>Tumor cells have adapted mechanisms for evading the immune system, making this effort a challenge. Different types of cancer cells have their own unique differences compared to normal healthy cells, and in order to recognize problematic cells, the immune system needs to recognize many potential changes (different palm tree patterns, ketchup vs mustard stains, etc). Early cancer vaccines were not widely effective because they could only recognize a few of these differences. </p>
<p>Researchers from Stanford University recently tested a new vaccine, composed of stem cells, that may help the immune system recognize many different tumor proteins and stimulate an immune response against several types of cancer.</p>
<p><strong>Vaccinating mice with iPS cells leads to an immune response against tumor cells</strong></p>
<p>Interestingly, tumor cells share properties with cells that are found in early development. Researchers wondered whether they could use embryonic-like stem cells as a vaccine to elicit an immune response against cancer cells. They engineered mouse skin cells in the laboratory to become induced pluripotent stem cells (<a href="http://www.closerlookatstemcells.org/patient-resources/stem-cell-glossary#ips-cells">iPS cells</a>), a process which causes mature cells to take on the characteristics of stem cells in the early embryo. These stem cells do indeed express many proteins that are found on tumor cells, making them intriguing candidates to use as a vaccine against tumor cells. Scientists wondered: if they vaccinated mice with stem cells, would T cells learn to recognize these proteins and be able to later attack the cancer cells that express them?</p>
<p>To test whether an iPS cell vaccine could be used to prevent cancerous cell growth, researchers stimulated the immune system of mice by first vaccinating them with irradiated iPS cells, and then injecting them with cancer cells (the irradiation serves to stop cell proliferation and prevents the iPS cells from forming tumors on their own). Strikingly, researchers found that mice that had been vaccinated with iPS cells initiated a strong immune response and had significantly less tumor progression compared to mice that weren&rsquo;t vaccinated. The iPS cell vaccine was able to protect the mice against breast, skin, and lung cancer. </p>
<p><strong>iPS cell vaccines may also prevent cancer recurrence</strong></p>
<p>Surgery is a common treatment for cancer in humans, and although surgeons do their best to remove the entire tumor, in many cases a few cancer cells remain. If those cells are able to regrow over time, they may become another tumor, causing cancer recurrence. To test whether the iPS cell vaccine could be used to prevent cancer from recurring, scientists vaccinated mice with irradiated iPS cells after tumor removal. Researchers found that mice vaccinated with iPS cells after surgery were able to illicit an immune response and had significantly less tumor recurrence after surgery compared to mice that weren&rsquo;t vaccinated.&nbsp; </p>
<p><strong>Can the vaccines work in humans? The need for further study</strong></p>
<p>The initial results of these studies in mice are promising, with evidence that an individual&rsquo;s own cells can be engineered to make a robust vaccine against tumor cells, using the body&rsquo;s natural immune system to fight cancer. This proof-of-principle study in mice is just the first step in testing the use of iPS cells as a cancer vaccine. If promising results continue, the vaccine may then be tested in humans in a series of clinical trials, which can take 10 to 12 years. </p>
<p>A single universal cancer treatment to prevent all cancer types has been the pinnacle goal of cancer research for decades. Unexpectedly, the answer could possibly lie in a stem cell vaccine. These remarkable preliminary results are sure to inspire many more studies as researchers work to confirm and further these compelling new findings.</p>

Can Stem Cell-Based Treatments Provide a Durable Treatment for Parkinson’s Disease?

<p>April is Parkinson&rsquo;s Awareness Month, a time intended to raise the visibility of a disease that effects an estimated five to ten million people world-wide and to share its personal, societal, and scientific impact. </p>
<p>The medical community has been &ldquo;aware&rdquo; of this disease since its published description by James Parkinson in 1817. Let that sink in! Physicians and scientists have spent at least the last two centuries trying to understand, treat and cure what was initially described as &ldquo;paralysis agitans,&rdquo; or shaking palsy. Are we finally getting closer to a durable treatment or potentially a cure? &nbsp;</p>
<p>Parkinson&rsquo;s disease, as we know it today, is a progressive, degenerative disorder of the brain characterized by a resting tremor, slowness of movement, limb rigidity, and problems with gait and balance, though symptoms can vary among individuals. The disease occurs primarily in the aged brain, although an estimated 4% are diagnosed before age 50. </p>
<p>The pathology underlying Parkinson&rsquo;s is complex, but the critical defect appears to be the loss of a discrete population of neurons in the brain that produce dopamine, a chemical messenger released by neurons also known as a neurotransmitter, that is important in the coordination of movement. While these neurons comprise less than 0.001% of the estimated 85 billion neurons in the brain, their loss has a significant functional impact. Unfortunately, the underlying disease process that leads to the loss of these cells is not well known. </p>
<p>Because dopamine has such a critical role in Parkinson&rsquo;s disease, researchers have sought to determine whether treatments that restore or replace this neurochemical in the brain can treat disease symptoms. Over the past four decades researchers have tried to treat Parkinson&rsquo;s by replacing the lost neurons themselves, or the dopamine produced by this specific population of neurons.</p>
<p>&nbsp;One approach that has had success is the use of L-Dopa, a chemical precursor to dopamine that upon entering the brain is converted into dopamine. This medication has provided relief to patients with Parkinson&rsquo;s but it has limitations, including the potential for significant side effects such as abnormal heart rhythm, altered mental status, aggressive behavior, to name a few, and patients may develop resistance to the drug&rsquo;s effects over time. These issues make the long-term use of L-Dopa unsustainable for most patients. </p>
<p>While advances in drug development are improving the use of L-Dopa, another approach to treat Parkinson&rsquo;s is the replacement of dopamine-secreting neurons via cellular replacement therapy. The rationale behind this approach is that the defective cells can be replaced by healthy ones that, upon transplantation into the proper area, will form connections with existing cells and then secrete dopamine locally and restore normal movement. </p>
<p>While several cell types have been tested for their ability to treat Parkinson&rsquo;s symptoms, clinical trials conducted in the 1980s using fetal neurons have provided proof-of-principle that this approach can work in humans. An analysis of patients 20 years after receiving this treatment suggested that cellular replacement therapy could provide durable relief of symptoms for some, though not all, patients. It should be noted that at the time of the trial a pure population of dopamine-producing neurons could not be obtained, so a variable mixture of immature fetal cells was used in the transplant. It&rsquo;s not known whether a more defined population of cells might produce more robust and consistent relief.</p>
<p>As time advances, so usually does technology. The use of <a href="http://www.closerlookatstemcells.org/patient-resources/stem-cell-glossary#pluripotent-stem-cells">pluripotent stem cells</a> &nbsp;provides a more precise approach to generate a highly enriched population of dopamine-secreting neurons for replacement cell therapy. Pluripotent stem cells such as <a href="http://www.closerlookatstemcells.org/patient-resources/stem-cell-glossary#embryonic-stem-cell">embryonic stem cells</a> or <a href="http://www.closerlookatstemcells.org/patient-resources/stem-cell-glossary#ips-cells">induced pluripotent stem (iPS) cells</a>can be specialized in a laboratory to become dopamine-producing neurons in high numbers and at high purity. These pluripotent-derived dopaminergic neurons have proven effective at ameliorating symptoms in animal models of Parkinson&rsquo;s disease, but they have not yet been tested in humans. The ultimate test of this approach and its effectiveness will be assessed in rigorous clinical trials conducted around the world. </p>
<p>In addition to developing potential cellular replacement therapies, stem cells also can be used to model Parkinson&rsquo;s disease and better understand what&rsquo;s causing the loss of these neurons, an insight that could lead to a cure. For example, human iPS cells derived from Parkinson&rsquo;s patients and converted into neurons that produce dopamine can be used to identify and understand the role of specific genes in the development of Parkinson&rsquo;s disease. This includes looking for mutations that lead to Parkinson&rsquo;s-like effects to screening drugs that could be used to treat the disease.</p>
<p>The hope is that the advances in stem cells and cellular therapy, along with other approaches, have brought us to the doorstep of a durable treatment for Parkinson&rsquo;s disease. Although curing Parkinson&rsquo;s will require significant advances in our understanding of the disease and what triggers it, biomedical science is making strides in advancing treatments and improving patients&rsquo; lives. </p>

What Can We Learn from the (Tasmanian) Devil?

<p>Why might stem cell scientists care about a small marsupial unique to Tasmania, a small island off the coast of Australia? Good question. Tasmanian devils are afflicted with a unique type of cancer that is transmitted from animal to animal &ndash; a disease that is threatening existence of the species. Scientists are studying stem cells from these animals in the hopes that they can learn how the cancer spreads and develop life-saving treatments to save this marsupial from extinction.&nbsp;</p>
<p>Studying stem cells to learn about disease is integral to the work of stem cell scientists, who will soon be gathering across the Bass Straight from Tasmania in Melbourne, Australia for the <a href="http://www.isscr.org/meetings-events/annual-meetings/isscr-annual-meeting-2018/program/speakers-topics" target="_blank">International Society for Stem Cell Research (ISSCR) 2018 Annual Meeting</a>. Nearly 3500 researchers from around the world will be on hand to report and discuss the latest findings in stem cell research. The meeting highlights the diverse ways that stem cells are being studied and applied, with an eye toward insights that can improve human health. </p>
<p>While the meeting location is coincidental, it is does highlight the importance of studying stem cells in a wide variety of living organisms. About 70% of living marsupial species reside on the Australian continent. They are a type of mammal named for their distinctive pouch that some use to carry and protect their developing young, and many species face extinction. Notably, Tasmanian devils have experienced an 80% decline in population over the last 20 years, decimated by devil facial tumor disease (DFTD), a form of transmissible cancer passed between animals, with no known cure. </p>
<p>Transmissible tumors are extremely rare. In order to infect another animal with cancer the tumor cells need the ability to do two things: pass between individuals and evade the new host&rsquo;s immune system. To date, the only other types of transmissible cancer that have been identified are canine transmissible venereal tumors and a recently described cancer in soft-shell crabs. </p>
<p>Tasmanian devils spread DFTD when they bite each other during feeding or mating, passing along the tumor cells. In most mammals the infected cells would be rejected because the recipient&rsquo;s immune system would recognize them as foreign and eliminate them. In Tasmanian devils, however, it appears that the tumor cells use escape mechanisms to evade immune attack. The cells suppress expression of some key genes that would normally identify the tumor cells as foreign invaders to be destroyed. In the absence of these signals, the tumor cells multiply and continue to spread between animals. While transmissible cancers have not been detected in humans, tumor cells from cancers such as melanoma and breast carcinoma can escape immune response using these and other mechanisms. </p>
<p>In order to understand this disease and to try to develop treatments to help Tasmanian devils survive, scientists are using induced pluripotent stem (iPS) cells. These cells are created in the lab, using cells that normally cannot become another type of cell, such as skin cells, and engineering them to acquire &ldquo;stemness,&rdquo; the ability to become any type of cell. These iPS cells have been generated from a number of non-marsupial mammals, but it was unknown whether they could be made from marsupials until recently when a group of scientists at the University of Queensland, Australia, successfully generated marsupial iPS cells for the first time (see this <a href="http://" target="_blank"></a><a href="https://www.eurekalert.org/pub_releases/2018-02/maf-scr020818.php">EurekAlert! article</a> for more). </p>
<p>As researchers uncover how the DFTD tumors form and escape detection, they hope to develop iPS cell-derived treatments that could target the tumors and stop them from growing and being transmitted. This same research may one day lead scientists to identify novel cancer therapeutics for use in humans. </p>
The study of different animal species, such as the Tasmanian devil, is an essential aspect of scientific discovery; stem cells from one species can often shed light on the developmental biology and disease in another type of living organism. A focus on animals at risk of extinction, such as the Tasmanian devil, is also not new. iPS cells have been generated from endangered species such as the orangutan, snow leopard, and northern white rhinoceros, of which there are only 3 left in existence. Scientists hope that studying these iPS cells will illuminate the biology that makes each of these species unique and will enable regenerative medicine efforts that might help dwindling populations recover from genetic or metabolic diseases. By understanding more about these distinctive animals, and looking for similarities with aspects of human biology, researchers can also gain insights into how to address human disease.

Novel Stem Cell Therapy Grows New Skin

Imagine skin so fragile that rubbing or scratching it can lead to severe blistering and massive wounds. Patients with a rare genetic disease known as junctional epidermolysis bullosa (JEB) suffer from just this painful phenomenon. JEB patients have mutations in a protein known as laminin-332, which is necessary to physically attach the top layer of skin to the lower layers. When this protein is not functional, friction, such as that from rubbing or scratching, can separate these layers and form blisters which may compromise critical skin functions such as protection, regulation, and sensation. There is no known cure for JEB, and while patients with the most severe form of JEB occasionally survive into their teens, the majority die from this disease during their first year of life.
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<p><strong>Treatment Breakthrough<br />
</strong>In a clinical breakthrough, a team led by Michele de Luca from the Center for Regenerative Medicine in Modena, Italy recently <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Regeneration+of+the+entire+human+epidermis+using+transgenic+stem+cells" target="_blank">published</a> a treatment for JEB in the journal <em>Nature</em>. Researchers isolated stem cells from a JEB patient and repaired them by adding a corrected form of the mutated gene. In the lab, they grew sheets of healthy skin from the repaired cells, which, stunningly, were used to replace the majority of the patient&rsquo;s skin (<a href="https://www.statnews.com/2017/11/08/stem-cells-epidermolysis-bullosa/" target="_blank">see this <em>STAT</em> article for a detailed description</a>).&nbsp;</p>
<p>This first-of-its-kind treatment was performed on a 7-year-old boy with severe JEB who had lost approximately 80% of his skin. Doctors treating this young patient had exhausted all approved medical options and successfully petitioned the ethical review board at Ruhr-University in Bochum, Germany to approve the compassionate use of this experimental cell and gene therapy for this single patient. </p>
<p>The treatment began by obtaining cells from a biopsy of the boy&rsquo;s unblistered skin. These cells then received a functional version of the laminin gene through a gene therapy procedure. Genetically-corrected cells were then expanded in the laboratory to form sheets of skin to obtain the nearly 400 million cells that were grafted onto the patient. </p>
<p>Within a month of transplanting the skin grafts, the patient exhibited nearly complete restoration of all the affected areas. At the conclusion of the study, almost two years later, the regenerated skin was firmly adhered to the underlying layers, exhibiting molecular markers of normal skin, and withstanding stress without blistering. In this groundbreaking achievement, a combination of cell and gene therapy restored the function of a critical protein, which enabled regeneration of 80% of the patient&rsquo;s skin.&nbsp; </p>
<p><strong>Skin Regeneration<br />
</strong>Skin is the largest organ in the body and has many critical functions. It is a barrier that helps regulate temperature and hydration levels, sense the environment, and offer protection from infection and physical damage. Skin cells in the epidermis, or outer layer of skin, naturally slough off and are constantly being replaced. Skin cells are replenished by epidermal stem cells, which can produce all of the cell types that make up the skin, including hair follicles and sweat glands.</p>
<p>While researchers knew that stem cells replenish the skin during normal growth and aging, prior to this study researchers did not know what cell type was responsible for driving regeneration during a skin transplant. Epidermal stem cells have been grown in the lab for decades, but they have not been shown to incorporate into a patient&rsquo;s skin and generate the full complement of cell types. &nbsp;</p>
<p>To determine which cell type drives regeneration during a skin transplant, scientists analyzed the regenerated skin over the course of eight months. While most of the nearly 400 million transplanted cells died after the procedure, the long-lived epidermal stem cells were found to be those responsible for sustaining the skin graft and the long-term maintenance and regeneration of the patient&rsquo;s skin<em> (see </em><em><a href="https://www.closerlookatstemcells.org/blog/blog/2018/01/09/Better-Defining-Blood-Stem-Cells-to-Help-Refine-Treatments" target="_blank"></a><a href="http://www.closerlookatstemcells.org/blog/blog/2018/01/09/Better-Defining-Blood-Stem-Cells-to-Help-Refine-Treatments"><em>January 2018 blog post</em></a><em> </em>&nbsp;for similar findings about blood stem cells in transplantation)</em>.</p>
<p><strong>Moving Forward After Proof-of-Principle Success<br />
</strong>The success of this gene and cell therapy treatment is a significant breakthrough, with important implications for the future use of these technologies. This proof-of-principle study involved only one patient, however, and additional <a href="http://www.closerlookatstemcells.org/from-lab-to-you/about-clinical-trials" target="_blank">clinical studies</a> need to be performed so that results can be replicated and long-term safety assessed before this treatment is routinely used in the clinic. While one potential long-term risk of this treatment is the formation of cancer, this patient has not developed tumors to date.</p>
<p>Based on this initial success, researchers hope that this type of gene therapy has the potential to prevent, rather than repair, skin blistering in JEB patients. One day this novel therapy may be able to cure patients with a variety of types of epidermolysis bullosa, helping them regain a normal quality of life. </p>
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