Dr. Milica Radisic is a Professor and Canada Research Chair at the University of Toronto. Her lab uses organ-on-a-chip engineering to mimic physiology of the heart, kidney, and vasculature for the purpose of modeling human disease and discovering more effective drugs. In this episode, she talks about the challenges of studying the heart and strategies to mature cardiomyocytes. She also discusses using macrophages to vascularize heart-on-a-chip platforms and enhance cardiac tissue function, sustainability considerations for microfluidic chips, and how these disease models can reduce the use of lab animals. Finally, she talks about starting a company to commercialize her lab’s cardiac chip platform, the landscape for women entrepreneurs, and advice from her mentor, Dr. Bob Langer.

Human Fetal Pancreas Development – A human fetal tripotent stem/progenitor cell can expand in vitro and can generate all three pancreatic cell lineages.

Hematopoiesis over the Human Lifespan – Researchers profiled individual transcriptome states of human hematopoietic stem and progenitor cells spanning gestation, maturation, and aging.

Intestinal Homeostasis – Intestinal stem cell PIEZO channels sense changes in stiffness and stretching, which controls stem cell behavior.

Cancer Risk in Aging – Aging of stem cells reduces their potential for tumorigenesis.

Image courtesy of Dr. Milica Radisic

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Dr. Cynthia “Cindy” Dunbar is National Institutes of Health (NIH) Distinguished Investigator and Chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute of the NIH. She talks about using macaques to study hematopoiesis and aging, and the challenges and considerations for using these models. She also discusses her collaborative study transplanting iPSC-derived cardiomyocytes into rhesus macaques, as well as the NIH’s unique research environment and her musical talents outside of the lab.

Enhancers in Neurogenesis – INST10 promotes epigenetic changes and transcription factor binding at enhancers that drive neural cell fate commitment.

Hepatoblastoma Organoids – Researchers studied the molecular and drug sensitivity landscapes of hepatoblastomas and tumor-derived organoids.

Sea Anemone Regeneration – In Nematostella vectensis, local regeneration triggers a systemic homeostatic response, leading to coordinated whole-body remodeling.

iPSC-Derived Human Venous Endothelial Cells – Scientists developed a model of vascular malformations and identified potential drug treatments.

Image courtesy of Dr. Cynthia Dunbar

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Dr. Mansi Srivastava is Professor of Organismic and Evolutionary Biology at Harvard University and Curator of Invertebrate Zoology at the Harvard Museum of Comparative Zoology. Her lab uses distantly related species to study evolution and regeneration. She talks about establishing Hofstenia miamia, or the three-banded panther worm, as a model system. She also discusses her lab’s work on adult stem cell lineage tracing and whole-body regeneration in Hofstenia, as well as her scientific outreach efforts.

Corneal Cell Therapy – Researchers used human iPSC-derived epithelial cell sheets to repair the corneas of patients with limbal stem cell deficiency.

A Vascular Atlas – A vascular cell atlas identifies angiotypic and organotypic characteristics of endothelial and mural cells.

Transcription Factors Before Animal Evolution – Sox and POU transcription factors emerged before the origin of animals.

NODAL Signaling in Embryo Development – NODAL signaling is active in the human blastocyst, but is not required to initiate or maintain the pluripotent epiblast.

Image courtesy of Dr. Mansi Srivastava

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Drs. Dina Radenkovic and Bruna Paulsen are Co-Founder & CEO and VP of Manufacturing and Therapeutic development at Gameto, a biotech company developing treatment solutions to improve women’s reproductive health. Their lead platform, Fertilo, uses ovarian support cells to mature oocytes outside of the body with the goal of making IVF and egg freezing shorter, safer, and more effective.

Sleep Speeds Healing  – Immune cells that promote sleep are recruited to the brain after myocardial infarction.

Epigenetic Regulators of iPSC-T Cell Differentiation – CAR iPSC-T cells derived via G9a/GLP inhibition display enhanced antitumor activity.

Minimizing Off-Target Toxicity – Researchers identified carbonic anhydrase 12 as a druggable target for doxorubicin-induced cardiotoxicity.

Cell Division in Differentiation – Researchers have shown that cell state transitions are decoupled from cell division during early embryo development.

Images courtesy of Drs. Dina Radenkovic and Bruna Paulsen

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Dr. Meritxell Huch is a Scientific Director at the Max Planck Institute of Molecular Cell Biology and Genetics and an Honorary Professor at the Technical University of Dresden. Her research focuses on liver and pancreas organoid models.  She discusses a protocol for liver mesenchyme and ductal cell organoid co-culture and generating bipotent stem cells from the liver. She also tells her story of moving throughout Europe to pursue her scientific passions.

A Zebrafish Developmental Atlas – Zebrahub is a transcriptional and spatiotemporal resource of zebrafish development.

Fertilization in Zebrafish and Humans – A conserved sperm complex binds to divergent egg proteins in mice and mammals to mediate sperm-egg interaction.

Dedifferentiation and Limb Progenitors – Chemically-induced dedifferentiation generates progenitor-like cells similar to human embryonic limb bud progenitors.

Yamanaka Factors in Neurodegeneration – Scientists induced Yamanaka factors in a mouse model of Alzheimer’s disease.

Image courtesy of Dr. Meritxell Huch

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Dr. Samantha Morris is an Associate Professor of Medicine at Brigham and Women’s Hospital and Associate Professor of Systems Biology at Harvard Medical School. She talks about dissecting and manipulating the genetic pathways that regulate cell identity. She discusses tools to measure cell fate transitions and incorporating in silico and in vitro experiments.

A Prenatal Skin Atlas – A skin atlas revealed that crosstalk between non-immune and immune cells underpins the formation of hair follicles.

Human Pancreatic Differentiation – Researchers used single-nucleus RNA sequencing to characterize the human fetal pancreatic microenvironment.

A Cardiac Fibrosis Therapeutic Target – High-throughput screening in iPSC-derived cardiac fibroblasts identified MD2 as a therapeutic target for cardiac fibrosis.

Mammalian Gastrulation – Scientists identified a link between the pathways that produce energy for embryo growth and the systems that regulate cell specialization.

Image courtesy of Dr. Samantha Morris

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Dr. Alfonso Martinez Arias is the CREA Research Professor in the Department of Systems Bioengineering of the Universitat Pompeu Fabra in Barcelona. He talks about his path to developmental biology research and developing gastruloids to model human development. He also discusses standards for embryo models and his recent research on hematopoiesis.

Tuft Cell Regeneration – Human tuft cells can survive irradiation damage and retain the ability to generate all other epithelial cell types.

Heart-Forming Organoids – hPSC-derived heart-forming organoids recapitulate aspects of heart, vasculature, and foregut co-developments.

Neural Stem Cell Aging – A CRISPR screen revealed genetic interventions that boost the function of old neural stem cells.

Symmetry Breaking in Gastruloids – Researchers used synthetic ‘signal-recording’ gene circuits to trace the evolution of signaling patterns in gastruloids.

Image courtesy of Dr. Alfonso Martinez Arias

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Dr. Behzad Yeganeh is an Associate Scientist at the Children’s Hospital of Eastern Ontario Research Institute and the University of Ottawa. His work focuses on lung development and injury. He talks about neonatal lung diseases and the mechanisms that regulate autophagy and apoptosis.

Cell Therapy for Type 1 Diabetes – Chemically induced PSC-derived islets were transplanted into a patient and led to insulin-independent glycemic control.

Giant Panda iPSCs – Primary fibroblast cells were isolated from the giant panda and used to generate iPSCs.

Pausing Blastocyst Development – Human blastoids under mTOR inhibition show a diapause-like response.

Sustaining Epithelial Cultures – Epithelioids are a facile, cost-effective method of culturing multiple mouse and human epithelia

Image courtesy of Dr. Behzad Yeganeh

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Dr. Dmitriy Sheyn is an Associate Professor in the Department of Orthopedics and Regenerative Medicine Institute at Cedars-Sinai Medical Center. His lab focuses on the development of stem cell therapies for multiple musculoskeletal disorders caused by acute injuries and aging. He talks about ways to model disc degeneration and tendon injuries. He also discuses his lab’s work on tendon differentiation and the mechanisms of low back pain.

Skin Transparency for Live Imaging – Researchers used tartrazine to make the skin of a live rodent temporarily transparent.

Muscle Regeneration – Scientists generated satellite cells from skeletal muscle tissue and transplanted them into mouse muscle.

Cardiac Assembloids – Scientists used PSC-derived cardiac assembloids to model the atrioventricular conduction axis and study complex disorders affecting heart rhythm.

Yamanaka Factors and Cellular Senescence – Partial cellular reprogramming improved health markers in mouse models of aging.

Image courtesy of Dr. Dmitriy Sheyn

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Dr. Ludovic Vallier is the W3 Einstein Strategic Professor for Stem Cells in Regenerative Therapies at the Berlin Institute of Health and a Max Planck Fellow at the Max Planck Institute for Molecular Genetics. His lab uses stem cells to model embryonic development in vitro and to produce liver cells with an interest for cell therapy. He talks about modeling non-alcoholic fatty liver disease and his lab’s pivot to SARS-CoV-2 research early in the pandemic. He also discusses how iPSCs could be used to regenerate the liver after injury.

Enhancing Compatibility in Interspecies Chimeras – Researchers used nanobody-antigen interactions to increase the chimerism of human PSCs in mouse embryos.

Single-Nucleotide RNA Sequencing for Brain Aging – Scientists uncovered different cellular trajectories and cell communities in Alzheimer’s disease and normal aging.

Glial Cells in Multiple Sclerosis – iPSC-derived multiple sclerosis models provide a unique platform for dissecting glial contributions to disease phenotypes.

Organoids to Model Spinal Trigeminal Nucleus Development – Scientists differentiated hPSCs into region-specific brain organoids.

Image courtesy of Dr. Ludovic Vallier

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