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="">CRISPR babies</a>,&rdquo; named for the <a href="">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="">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="">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="">recent report from the Nuffield Group</a>, such as: </p>
<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>
<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>
<li>The World Health Organization has convened an <a href="">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="">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="">an international governance framework</a> and along with another group called for a <a href="">moratorium on any clinical embryonic genome manipulation</a> &ldquo;until serious scientific, societal, and ethical concerns are fully addressed.&rdquo; </li>
<li><a href="">Individual countries</a> are proposing tightening regulations around gene editing research. </li>
<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</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="">Michael J. Fox Foundation</a> and the <a href="">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="">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="">embryonic stem cells</a> and could become any cell type in the body. These cells are known as &lsquo;<a href="">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="">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="" 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>
<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="">Parkinson&rsquo;s Disease</a> patient brains, different cell types of the eye for <a href="">degenerative eye conditions</a>, <a href="">heart cells for heart disease</a>, and more. </li>
<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="" 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="">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="">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="">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="">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>
<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>
<p>Patients should be cautious of<a href=""> 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="">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>

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="">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="">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="">zebrafish</a>, as many as 92,000 cells from <a href="">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="">development of a whole mouse</a>. Together, studies over the last year have revealed:</p>
<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>
<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>

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>
<br />
<img src="" 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="">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="">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="">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="">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="">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="">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=";" 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="" 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="" target="_blank">blood disorders</a>, cystic fibrosis, <a href="" 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="" 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="" 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="">recent public forum</a> in Melbourne, Australia, &ldquo;<a href=";" 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 />
<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 />
<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 />
<br />