Epigenetic clocks based on tissue DNA methylation analysis have emerged as robust and powerful biomarkers of aging. This technology has allowed scientists to investigate how diseases affect the aging process, to evaluate the effectiveness of therapeutic aging interventions, and to correlate age with overall health among the general public. Today you can even purchase test kits online that enable you to measure your own biological age. However, despite the growing use of epigenetic clocks in research, surprisingly little is known about the aging clock’s cellular underpinnings. For example, it remains unclear whether all cells within a tissue exhibit the same epigenetic age, and whether age-related cellular heterogeneity within a tissue affects the epigenetic clock. This is particularly relevant in regenerative tissues maintained by a hierarchy of stem, progenitor, and differentiated cells, all of which may change their frequencies within a tissue with age. The guests on today’s podcast tackle this important question through analyses of immature and mature cell populations from muscle, blood, and epithelia, using three different epigenetic clocks widely used in the field. They discuss their results, and the implications for the interpretation of existing clocks, and the development of more sensitive and accurate clocks.

Guests
Konrad Hochedlinger, PhD, Massachusetts General Hospital and Harvard Stem Cell Institute, MA, USA

Rebecca Gorelov, PhD, Harvard Medical School, USA

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
X: @martinperaJAX

Supporting Paper
Dissecting the impact of differentiation stage, replicative history, and cell type composition in epigenetic clocks, Stem Cell Reports

About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.
X: @StemCellReports

About ISSCR
With nearly 5,000 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

Those who study neurological diseases and their underlying cellular and molecular mechanisms have a number of scientific models at their disposal. In vivo animal models, particularly those bearing targeted genetic modifications, remain the gold standard, especially when it comes to assessment of behavioral readouts and neurobiological disease mechanisms in vivo. Historically, animal models have been widely used for preclinical validation of drug efficacy and safety.

Increasingly there is a move away from this approach, and human cellular models using induced pluripotent stem cells and their derivatives such as three-dimensional organoid models have recently provided unprecedented genetic and mechanistic insights into disease mechanisms. Human/animal chimeras made by xenografting human cells into the animal brain have unparalleled potential to study human cells in the context of the whole organism. Our guests today review the use of these types of model systems to understand neuropsychiatric diseases, focusing on Alzheimer’s and Parkinson’s disease, epilepsy, Down syndrome, and schizophrenia and provide critical appraisal of the impact of human-rodent xenografting approaches for advancing our understanding of those diseases and brain development.

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
@martinperaJAX

Guests
Giuseppe Testa, MD, PhD, Università Statale, Human Technopole, and the European Institute of Oncology, Italy

Marlene Pereira, PhD UCB Pharma, Brussels, Belgium

Reinald Shyti, PhD, Human Technopole and the European Institute of Oncology, Italy

Supporting Content
In and out: benchmarking in vitro, in vivo, ex vivo and xenografting approaches for an integrative brain disease modeling pipeline, Stem Cell Reports

About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.
Twitter: @StemCellReports

About ISSCR
With nearly 5,000 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

This episode of The Stem Cell Report will discuss the process of directing stem cells to acquire the proper identity, an essential step in the development of effective and durable cell replacement therapies. Specifically, we will talk about the process of directing cells into a ventral mesencephalic dopaminergic fate for treating Parkinson’s disease.

Guests
Agnete Kirkeby is an Associate Professor in the Department of Neuroscience at the University of Copenhagen, a Principal Investigator with the Novo Nordisk Foundation Center for Stem Cell Medicine renew, and a Principal Investigator at the Wallenberg Center for Molecular Medicine at Lund University. Professor Kirkeby led the preclinical development of a stem cell-based therapy for Parkinson’s Disease which was approved for a first-in-human clinical trial in Sweden. Agnete also co-chairs the ISSCR 2024 Annual Meeting Program Committee, the group responsible for planning the upcoming meeting this July in Hamburg, Germany.

Pedro Rifes received his PhD from the Universidade de Lisboa in Portugal and was a postdoctoral scholar in the Kirkeby Laboratory. He served as an Adjunct Assistant Professor at the University of Copenhagen and is currently a Project Manager at Bioneer A/S, a Danish specialty Contract Research Organization. Connect with him on LinkedIn.

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
@martinperaJAX

Supporting Content
Paper link: Forced LMX1A expression induces dorsal neural lolfates and disrupts patterning of human embryonic stem cells into ventral midbrain dopaminergic neurons, Stem Cell Reports

About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports

About ISSCR
With nearly 5,000 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

Myelination is one of the last events during mammalian brain development and is thought to continue into young adulthood in humans. Even in adulthood, ongoing low-level myelination is essential for neural homeostasis, and for dynamic processes such as learning and memory. Deficits in myelination resulting in abnormal white matter and disruption of neuronal function are observed in a wide variety of disorders of the CNS. One strategy for alleviating these deficits is to enhance the genesis of myelin-forming oligodendrocytes from their upstream precursor parents, oligodendrocyte precursor cells (OPCs). However, the capability of these OPCs to contribute to remyelination in injury or disease in the adult CNS remains unclear. To better understand adult oligodendrogenesis and remyelination, our guests today characterized and compared murine OPCs during early postnatal myelination with those from adult injury-induced adult remyelination. Their findings identify two developing OPC groups subserving distinct postnatal functions and suggest that neonatal and adult OPC-mediated oligodendrogenesis are fundamentally different, The findings have important implications for therapeutic interventions aimed at myelin repair.

Guests
Freda Miller, PhD, Michael Smith Laboratories, The University of British Columbia
Beatrix Wang, BSC, PhD candidate, The University of British Columbia and The University of Toronto

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
@martinperaJAX

Supporting Content
Single-cell approaches define two groups of mammalian oligodendrocyte precursor cells and their evolution over developmental time, Stem Cell Reports

About Stem Cell Reports
Stem Cell Reports  is the open access, peer-reviewed journal of the International Society for Stem Cell Research communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports  focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports

About ISSCR
With nearly 5,000 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

Biomedical researchers have long sought ways to repair spinal cord damage with the holy grail of the pursuit being the reconstitution of lost function. In the mid 1990’s with the successful culture of human embryonic stem cells, and about a decade later induced pluripotent stem cells (iPSCs), the field was energized with a potential new approach to replace the lost neurons and glia cells and restoring neural connections. In the decades since that discovery some progress has been made, however many hurdles remain, including establishing a functional synaptic connection between the transplanted and host neurons which is crucial for motor function recovery. To boost therapeutic outcomes our guests tested an ex vivo gene therapy to promote synapse formation between the donor and host neurons by expressing the synthetic excitatory synapse organizer CPTX in hiPSCs-derived neural stem and progenitor cells. Tune in to learn what they discovered.

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
@martinperaJAX

Guests
Hideyuki Okano, MD, PhD Keio University, Japan, Professor in the Department of Physiology and Chairman of the Graduate School of Medicine at Keio University. Professor Okano has spent decades studying neurogenesis and is currently leading a first-of-its-kind cell therapy for spinal cord injury. He has previously served as an Associate Editor for Stem Cell Reports and is a member of the Editorial Board. He is the current President of the Japanese Society of Regenerative Medicine and Vice President of the ISSCR.

Yusuke Saijo, MD. Keio University, Japan, graduated from Kyorin University School of Medicine and following a two-year initial training period, he embarked on a clinical journey, working in the field of orthopedic surgery at Keio University, specializing in the spinal cord and spinal disorders. Dr. Yusuke currently works in the research laboratory led by Professors Okano and Masaya Nakamura, where his research focuses on ex vivo cell and gene therapy for spinal cord regeneration.

Supporting Content
Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury, Stem Cell Reports

About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.
Twitter: @StemCellReports

About ISSCR
With nearly 5,000 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scien

Collectively, retinal degenerative disorders are a major cause of blindness worldwide. For example, one of the most common disorders is age related macular degeneration, which alone affects nearly 200 million globally.

In humans, and other mammals, the loss of the retinal cells is an irreversible process. However, in some non-mammalian vertebrates like frogs and fish, retinal neurons can regenerate. This process is dependent upon Müller glia, which can re-enter the cell cycle and reprogram into neurogenic progenitors upon retinal injury or disease. Progress has been made in understanding the genetic program underlying these regenerative process, and proof-of-principle experiments in the adult mouse retina demonstrated that genetic programs in frog and fish can be coopted to induce neurogenesis in mammals. Our guests today have extended this research to genetically reprogram fetal or organoid-derived human Müller glia into retinal neurons. They will talk about this work, the background underlying it and its potential applications.

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
@martinperaJAX

Guests
Thomas Reh is a Professor of Biological Structure, and a member of Institute for Stem Cell and Regenerative Medicine at the University of Washington. His research is focused on understanding retinal disease in disorders such as glaucoma and macular degeneration, and on developing treatments for vision loss. The Reh laboratory studies regeneration in animal models, including invertebrates like frog and fish, to understand the key genes involved in endogenous regeneration. The ultimate goal of this research is to stimulate regeneration in the mammalian retina, and ultimately to restore sight in patients.

Juliette Wohlschlegel is a postdoctoral scholar in the Reh laboratory. Dr. Wohlschlegel received her undergraduate degree in neuroscience from the Sorbonne Université, and her PhD from Institut de la Vision in France, where she studied inherited retinal diseases.

Supporting Content
ASCL1 induces neurogenesis in human Müller glia, Stem Cell Reports

About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.
Twitter: @StemCellReports

About ISSCR
With nearly 5,000 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

Since the 1930’s research using human fetal tissue has been used in numerous scientific and medical advances that have saved millions of lives, including the development of vaccines and treatments for diseases. Despite its substantial contribution to medicine and science, significant public debate and misinformation persists surrounding the ethical use of human fetal tissue in biomedical research.

The ISSCR, led by its Public Policy Committee, have been tireless champions and advocates for sound science policy across the globe. This includes advocacy for fetal tissue research and working to inform policymakers and the public on the vast medical applications and advances that have, and will, come from the use of HFT in biomedical research. Towards that end, the ISSCR and the Lawrence Goldstein Policy Fellows have authored a recent paper in Stem Cell Reports entitled, Human Fetal Tissue is Critical for Biomedical Research.

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
@martinperaJAX

Guests
Lawrence (Larry) Goldstein, PhD, is a Distinguished Professor Emeritus, Department of Cellular and Molecular Medicine and Director Emeritus of Stem Cell Program at the University of California, San Diego. He is the namesake for the ISSCR’s Lawrence Goldstein Science Policy Fellowship which is training the next generation of scientists to impact public policy.

Tyler Lamb, JD, is the ISSCR’s Director of Policy and leads the Society’s global policy efforts.

Tamra Lysaght, PhD, University of Sydney, Australia, is an Associate Professor in Health Ethics.

Justin Brumbaugh, PhD, University of Colorado Boulder, USA, is an Assistant Professor in Molecular Cellular & Developmental Biology.

Supporting Materials
Drs. Brumbaugh, Lysaght, and Goldstein, along with Brian Aguado, are authors of the recently published paper, Human Fetal Tissue is Critical for Biomedical Research.

About Stem Cell Reports
Stem Cell Reports is the Open Access journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.
Twitter: @StemCellReports

About ISSCR
With more than 4,800 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

This November marks the 25th anniversary of the successful isolation and culture of human embryonic stem cells by Jamie Thompson. This breakthrough was a turning point in biomedical research. This discovery provided scientists with a limitless source of human cells to understand human biology and model disease. The discovery also provided a novel pathway to develop tissues and cells that could potentially be used to provide curative diseases like diabetes and Parkinson’s, among others. To date, numerous companies are advancing human embryonic stem cell-based therapies in over 50 approved and regulated clinical trials.

However, in parallel to the legitimate, approved clinical trials, the great promise of this field has in a sense fostered a plague of rapid and continuous growth in the marketing of unregulated and unproven treatments, via direct-to-consumer clinics across the globe. These predatory clinics offer so-called stem cell therapies to treat myriad conditions with approaches not supported by rigorous scientific evidence. During the pandemic these treatments expanded to include COVID-19, including the use of what’s being advertised as exosome therapy.

Guest
The guest on today’s podcast is an expert on the stem cell marketplace of unproven treatments. Leigh Turner is the Executive Director of the University of California Irvine Bioethics Program, and a Professor in the Program in Public Health’s Department of Health, Society, and Behavior. He is also a member of UCI’s Stem Cell Research Center. His current research addresses ethical, legal, and social issues related to stem cells and regenerative medicine products. Dr. Turner served on the task force that developed the ISSCR Guidelines for Stem Cell Research and Clinical Translation and is also a member of the ISSCR’s Ethics Committee. Dr. Turner and colleagues authored the recent paper in Stem Cell Reports entitled, Businesses Marketing Purported Stem Cell Treatments and Exosome Therapies for COVID-19: An Analysis of Direct-to-Consumer Online Advertising Claims.

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
@martinperaJAX

About Stem Cell Reports
Stem Cell Reports is the Open Access journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.
Twitter: @StemCellReports

About ISSCR
With more than 4,800 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff