The Stem Cell Report with Janet Rossant

• Movin’ On Out: Mobilizing HSCs From The Bone Marrow

  Hematopoietic stem cells (HSCs) normally reside in the bone marrow niche but can traffic across the bone marrow endothelium into the bloodstream to populate different niches. This process of HSC mobilization from the bone marrow to the blood, is an increasingly favored procedure to obtain HSCs for hematopoietic cell transplantation therapy. Though mobilization is robust in many donors due to years of refined protocols and drug combinations, the process remains difficult or contraindicated among substantial patient subgroups. Using the current standard of care, up to 30% of patients fail to mobilize HSCs and some patients cannot tolerate the current mobilization procedures. Today’s guests will discuss their research using vascular endothelial growth factor, known as VEGF, as an alternative method of mobilization, the mechanisms underlying it, and the implications for improving patient outcomes.GuestsStephanie Smith-Berdan, MS, Institute for the Biology of Stem Cells, Department of Biomolecular, Engineering, University of California, Santa Cruz, USA. Camilla Forsberg, PhD, Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California, Santa Cruz, USA. HostJanet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner FoundationSupporting ContentPaper link: Vascular endothelial growth factor-induced vascular permeability results in drastic and reversible hematopoietic stem cell mobilization, Stem Cell ReportsAbout Stem Cell ReportsStem 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: @StemCellReportsAbout ISSCRWith nearly 5,000 members from more than 80 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 StaffKeith Alm, Chief Executive OfficerYvonne Fisher, Managing Editor, Stem Cell ReportsKym Kilbourne, Director of Media and Strategic CommunicationsMegan Koch, Senior Marketing ManagerJack Mosher, Scientific DirectorHunter Reed, Senior Marketing Coordinator

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• Cancer Neuroscience, Tumor Organoids, and Understanding the Role of the Nervous System in Human Glioblastoma

  The role of neuronal influences on cancer pathogenesis and progression is increasingly appreciated in the nervous system. Neurons have been shown to enhance the proliferation and migration of gliomas, a glial-derived tumor of the CNS, via diffusible paracrine factors or synaptic inputs onto tumor cells. In glioblastomas, a highly aggressive glioma, mostly glutamatergic inputs have been identified. While the potential for glioblastomas to receive projections from neurons of other neurotransmitter subtypes, such as from cholinergic neurons, has recently been discovered in xenotransplantation models, whether synapses can form between human cholinergic neurons and glioblastoma cells and consequences of these inputs and other non-synaptic mechanisms are still unknown.   Human induced pluripotent stem cell-based models have been emerging as a powerful platform for studying human-specific disease mechanisms. Today’s guests developed a co-culture model for the study of neuron-tumor interactions by combining patient derived glioblastoma organoids and hiPSC-derived cholinergic neurons. They will discuss their recent findings and what it means for understanding and potentially treating a tumor for which there is no known cure. GuestsGuo-li Ming, MD, PhD, Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of PennsylvaniaHongjun Song, PhD, Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania Yusha Sun, Neuroscience Graduate Group, Perelman School of Medicine, University of PennsylvaniaHostJanet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner FoundationSupporting ContentPaper link:  Cholinergic neuron-to-glioblastoma synapses in a human iPSC-derived co-culture model, Stem Cell ReportsAbout Stem Cell ReportsStem 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: @StemCellReportsAbout ISSCRWith nearly 5,000 members from more than 80 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 StaffKeith Alm, Chief Executive OfficerYvonne Fisher, Managing Editor, Stem Cell ReportsKym Kilbourne, Director of Media and Strategic CommunicationsMegan Koch, Senior Marketing ManagerJack Mosher, Scientific DirectorHunter Reed, Senior Marketing Coordinator

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• Stem Cells in Space: Muscle Regeneration in Microgravity

  Skeletal muscle is one of the most abundant tissues in the human body, representing approximately 40% of body weight. Under certain circumstances, skeletal muscle can be regenerated through satellite cells, a reservoir of quiescent muscle stem cells, that can be activated with injury or in certain diseases and give rise to newly formed multi-nucleated myotubes and myofibers. However, the regenerative potential of muscle is diminished or is completely absent in the course of normal aging, certain diseases, and space travel. For example, time spent in microgravity can have a profound impact on human physiology, especially the muscular system, as astronauts lose up to 20% of their lean muscle mass and up to half of their strength.  The identification of countermeasures against the effects of muscle regeneration, including microgravity, is an increasing priority for an aging population and continued space travel. Experiments in microgravity, conducted on the International Space Station, offer a unique opportunity to understand muscle regeneration and the effects of microgravity. Our guests today will discuss muscle regeneration, their muscle-on-a-chip platform that mimics salient aspects of impaired muscle regeneration, and the feasibility of drug screening in microgravity.GuestsNgan Huang, PhD, Department of Cardiothoracic Surgery, Stanford University, USASoochi Kim, PhD, Department of Biotechnology and Bioinformatics, Korea University, KoreaHostJanet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner FoundationSupporting ContentPaper link:  Skeletal muscle-on-a-chip in microgravity as a platform for regeneration modeling and drug screeningAbout Stem Cell ReportsStem 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: @StemCellReportsAbout ISSCRWith nearly 5,000 members from more than 80 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 StaffKeith Alm, Chief Executive OfficerYvonne Fisher, Managing Editor, Stem Cell ReportsKym Kilbourne, Director of Media and Strategic CommunicationsMegan Koch, Senior Marketing ManagerJack Mosher, Scientific DirectorHunter Reed, Senior Marketing Coordinator

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• Parkinson's Disease, Cell Therapy, and Exercise

  The potential of pluripotent stem cells and the ability to scale and differentiate them to generate large numbers of enriched cell populations has created new opportunities and approaches to treat human disease. Preclinical proof-of-principle data demonstrates that stem cell-derived neural grafts can be used to reverse symptoms of multiple neurological conditions, including Parkinson’s Disease. Cell grafts enriched with dopaminergic neurons, can structurally and functionally integrate in the brain of Parkinson’s Disease models to reverse motor deficits, a finding which has launched several clinical trials. While the results in animal models is essential proof-of-concept, the survival and integration of these cells is suboptimal compared to treatments from fetal-derived ventral midbrain grafts.  An area of preclinical and clinical research showing promise in influencing neuronal survival and plasticity is exercise. The benefits of exercise on neural function and disease progression have been widely reported and they have also been shown to enhance the survival and integration of transplanted cells in models of some neurological diseases. However, there is limited data on the benefit of exercise on the functional outcomes of neural grafts in Parkinson’s Disease models. The guests on today’s program will discuss their recent study looking at the effect of exercise on cellular engraftment and functional recovery in animal models of Parkinson’s Disease and the implications for clinical outcomes. GuestsClare Parish, PhD, The Florey Institute of Neuroscience and Mental Health and University of Melbourne, Australia Niamh Moriarty, PhD, The Florey Institute of Neuroscience and Mental Health and University of Melbourne, AustraliaSupporting ContentPaper link: Exercise promotes the functional integration of human stem cell-derived neural grafts in a rodent model of Parkinson’s disease HostJanet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner FoundationAbout Stem Cell ReportsStem 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: @StemCellReportsAbout ISSCRWith nearly 5,000 members from more than 80 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 StaffKeith Alm, Chief Executive OfficerYvonne Fisher, Managing Editor, Stem Cell ReportsKym Kilbourne, Director of Media and Strategic CommunicationsMegan Koch, Senior Marketing ManagerJack Mosher, Scientific AdvisorHunter Reed, Senior Marketing Coordinator

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• Leaving an Imprint: The Function, Impact, and Detection of Epigenetic Marks

  Parent-specific epigenetic marks (imprints) leading to parent-specific gene expression are crucial for normal growth and development, yet their mechanisms of establishment and maintenance are not fully understood. In humans, approximately 200 imprinted genes have been discovered, and improper imprinting can manifest in growth restriction, obesity, intellectual disabilities, behavioral abnormalities, and an increased risk of certain cancers. While the use of pluripotent stem cells, especially those in the naïve state, have advanced aspects of modeling early development, a persistent issue hampering bona fide naïve hPSCs is the erosion of imprints. Our guests on today's episode will discuss genomic imprinting, its function, impact, and a new reporter system of imprinted gene expression in hPSCs that enables real-time visualization of loss-of-imprinting at single-cell resolution. This assay provides an important tool to help discover how to improve the imprint fidelity of naïve hPSCs and hence their application for studies of human development and regeneration. Guests Thorold Theunissen, PhD, Department of Developmental Biology, Washington University in St Louis, USA Gal Keshet, The Azrieli Center for Stem Cells and Genetic Research, The Hebrew University of Jerusalem, IsraelSupporting ContentTracking and mitigating imprint erasure during induction of naïve human pluripotency at single-cell resolutionHostJanet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner FoundationAbout Stem Cell ReportsStem 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: @StemCellReportsAbout ISSCRWith nearly 5,000 members from more than 80 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 StaffKeith Alm, Chief Executive OfficerYvonne Fisher, Managing Editor, Stem Cell ReportsKym Kilbourne, Director of Media and Strategic CommunicationsMegan Koch, Senior Marketing ManagerJack Mosher, Scientific AdvisorHunter Reed, Senior Marketing CoordinatorVoice WorkBen Snitkoff

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