The Stem Cell Podcast – Details, episodes & analysis

Guest:

Dr. Ziyuan Guo is an Assistant Professor of Pediatrics at the Center for Stem Cell & Organoid Medicine at Cincinnati Children’s Hospital. He talks about in vivo reprogramming and cell and gene therapy in neurodevelopmental and neurodegenerative disorders. He also discusses assembloids to model the blood-brain barrier and strategies for organoid vascularization.

Featured Products and Resources:

• Use STEMdiff Cerebral Organoid Kits to mimic early brain development.
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The Stem Cell Science Round Up

Modeling Celiac Disease – Scientists generated air–liquid interface duodenal organoids from celiac disease patients.

Intestinal Immuno-Organoids – Intestinal immuno-organoids can be used to study tissue-resident immune responses in tumorigenesis and other diseases.

Naive PSCs in the Blastocyst – A blastocyst motif substrate reverts mouse and human PSCs to a naive state in vitro.

Sensory Neuron Excitability – Schwann cell-secreted PGE2 promotes neuronal maturation and normal sensory function.

Image courtesy of Dr. Ziyuan Guo

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Guest:

Dr. Themasap Khan is the Vice President at Civilization Ventures, a venture capital firm that invests in genomics, diagnostics, digital health, AI, and personalized and regenerative medicine.  He leads the firm’s scientific due diligence and academic outreach programs. Dr. Khan earned his in PhD in stem cell biology and regenerative medicine in Dr. Sergiu Pasca’s lab at Stanford, where his research focused on genome engineering, cerebellar organoid models, and live imaging to elucidate biological mechanisms underlying neuropsychiatric disorders.

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The Stem Cell Science Round Up

Gene Therapy for Adenosine Deaminase (ADA) Deficiency – Scientists treated patients with ADA severe combined immunodeficiency with a lentiviral vector encoding human ADA, which led to high overall and event-free survival.

Lineage Tracing through Somatic Mutations – Researchers used somatic mutations in hematopoietic progenitors from human fetuses to study the divergence of embryonic and extra-embryonic tissues during development.

A Small Molecule Cocktail to Enhance Cell Survival – Scientists used high-throughput screening to identify a cocktail that improves the viability of hPSCs and differentiated cells by blocking several stress mechanisms.

2-Photon Live Imaging of Single Corneal Stem Cells  – Researchers identified discrete, functionally diverse stem cell niche compartments in the corneal limbus in the eyes of live mice.

Photo Reference: Courtesy of Dr. Themasap Khan

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Guest:

Dr. Johan Jakobsson is a Professor of Molecular Neurogenetics at the Lund Stem Cell Center. His research focuses on epigenetic mechanisms of the brain, including the role of microRNAs, long non-coding RNAs, and endogenous retroelements in neural stem cells and neurons.

Featured Products and Resources:

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The Stem Cell Science Round Up

Intestinal Organoids to Model Self-Organization – Researchers found that stem cell zones in intestinal organoid cultures are shaped by fission events, and that organoid inflation drives stem cell differentiation.

Wound Healing Without Scarring – Preventing Engrailed-1 activation during wound healing promotes skin regeneration with recovery of skin appendages, ultrastructure, and mechanical strength.

Differentiation Unmasks Hidden Aspects of Aging in Stem Cells – Scientists used single-cell RNA sequencing to study age-related changes in muscle stem cells and fibro-adipose progenitors, and found an energy barrier in myogenic differentiation.

Human-Monkey Chimeric Embryos  – Researchers demonstrated that hEPSCs survived, proliferated, and generated several peri- and early post-implantation cell lineages inside monkey embryos.

Photo Reference: Courtesy of Dr. Johan Jakobsson

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Guest:

Dr. Marinna Madrid is Co-Founder of Cellino, an early-stage biotechnology company seeking to make personalized, autologous cell therapies viable at large scale for the first time. Cellino’s platform combines label-free imaging and high-speed laser editing with machine learning to automate cell reprogramming, expansion, and differentiation in a closed cassette format, enabling thousands of patient samples to be processed in parallel in a single facility.

Featured Products and Resources:

• Keep current with the latest in cell therapy research with Cell Therapy News.
• Show the world what stem cell research looks like from your perspective by taking part in this year’s #StemCellfie contest.

The Stem Cell Science Round Up

Using IGF1 to Rescue HSCs from the Hallmarks of Aging – Researchers found that a decline in IGF1 in the bone marrow microenvironment initiates hematopoietic stem cell aging, and that direct stimulation with IGF1 could reverse this phenotype.

Krüppel-Like Factor 1 is Critical for Heart Regeneration in Zebrafish – Krüppel-Like Factor 1 stimulates new cardiomyocyte production by reprogramming gene networks that regulate cardiomyocyte differentiation and mitochondrial metabolism.

How Aneuploid Embryos Can Lead to Healthy Births – Scientists showed that mosaic embryos can be rescued through BMP4-dependent apoptosis of aneuploidy in the primary germ layers.

Patient-Derived Cervical Organoids  – Generated from a pap smear sample, cervical organoids can be used as an experimental platform for sexually transmitted infection and cervical cancer research.

Photo Reference: Courtesy of Dr. Marinna Madrid

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Guests:

Dr. Brenda Raud is a postdoctoral researcher at the Netherlands Cancer Institute. Her research focuses on T cell-based immunotherapies and immuno-oncology. Dr. Jason Goldsmith recently completed his postdoctoral fellowship at the University of Pennsylvania, and is now the Director of Donor Medical Sciences at Seres Therapeutics, a biotechnology company working to revolutionize treatment of a wide range of diseases by modulating the function of the human microbiome.

In addition to their work as researchers, Brenda and Jason are also hosts of the new Immunology Podcast, a sister podcast to the Stem Cell Podcast.

Featured Products and Resources:

• Explore scientific resources for your immunology research at the STEMCELL Technologies immunology learning center.
• Show the world what stem cell research looks like from your perspective by taking part in this year’s #StemCellfie contest.

The Stem Cell Science Round Up

Single-Cell Synthetic Organism with Less Than 500 Genes – Researchers fabricated an artificial single-cell organism that can grow and divide like a normal cell, giving them insights into which genes are required for cell growth and division.

Humanized Skeletal Muscle Grown in Pigs – Scientists generated human-pig chimeric embryos with humanized skeletal muscle, as well as intraspecies chimeric pig embryos that were carried to term.

A 3D Model for Macular Degeneration – Researchers developed a 3D iPSC model of the retinal pigment epithelium-choriocapillaris complex, a complex that is damaged in age-related macular degeneration.

Human Brain Expansion Driven by an Early Cell Shape Transition   – Scientists grew human and ape cerebral organoids and discovered a transition state that is characterized by a change in cell shape, regulated by ZEB2, and delayed in humans.

Photo Reference: Courtesy of Drs. Brenda Raud and Jason Goldsmith

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Guest:

Dr. Krishanu Saha is an Associate Professor in the Department of Biomedical Engineering at the University of Wisconsin-Madison. His lab utilizes quantitative and bioengineering methods including genome editing, biomanufacturing, and disease modeling to advance the next generation of cell and gene therapies.

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The Stem Cell Science Round Up

Growing Advanced Embryos Outside the Uterus – Researchers removed mouse embryos from the uterus at five days of gestation and grew them for six more days in roller culture systems, allowing them to reach advanced organogenesis.

Lacrimal Gland Organoids That “Cry” – Scientists established long-term 3D organoid cultures of human and mouse lacrimal glands and used neurotransmitters to induce tear secretion.

Generating Human “Blastoids” – Starting with either human ESCs or iPSCs, researchers used a three-dimensional culture strategy to generate blastocyst-like structures in vitro.

Reprogramming Fibroblasts into iBlastoids – Fibroblasts were reprogrammed in vitro into three-dimensional models of the human blastocyst, termed iBlastoids.

SARS-CoV-2-Induced Cardiac Damage in iPSC-Derived Heart Cells  – Scientists infected iPSC-derived cardiac cells with SARS-CoV-2 to better understand how the virus attacks the heart.

Cytokine Storms in Cardiac Organoids – Using SARS-CoV-2-infected cardiac organoids and mice, researchers found that bromodomain and extraterminal domain family inhibition reduced infection and cardiac damage.

Photo Reference: Courtesy of Dr. Krishanu Saha

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Guest:

Dr. Kelly Shepard is the Associate Director of Discovery and Translation at the California Institute for Regenerative Medicine (CIRM). CIRM was created by the voters of California in 2004. The agency funds stem cell research at institutions and companies throughout California with the goal of accelerating treatments to patients with unmet medical needs.

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The Stem Cell Science Round Up

Intestinal Organoids for Regeneration – Researchers have generated a functional small intestinalized colon using ileum-derived organoids, offering a possible strategy for short bowel syndrome treatment.

Gene Disrupts Lipid Homeostasis in Glia – Scientists have shown that APOE4 has widespread effects on the brain’s ability to metabolize lipids and respond to stress, offering an explanation for why the gene enhances Alzheimer’s risk.

Maturation of Year-Old Brain Organoids – 3D cultures of human brain cells kept alive for nearly a year have been shown to undergo transitions in gene activity that resemble those seen in newborns.

Brain Cell Grafts Reverse Parkinson’s Symptoms – Grafting neurons grown from a monkey’s own cells into their brain relieved the debilitating movement and depression symptoms associated with Parkinson’s disease.

Photo Reference: Courtesy of Dr. Kelly Shepard

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Guest:

Dr. Willy Lensch is Strategic Advisor to the Dean at Harvard Medical School. Previously Executive Director of the Harvard Department of Stem Cell and Regenerative Biology, his experience in research, education, administration, science policy, intellectual property, science consulting, and outreach have combined to support and advance stem cell science and discovery at Harvard.

Featured Products and Resources:

• Contest: Subscribe to Organoid News for a Chance to Win a Personalized Lab Coat
• STEMCELL Technologies Survey Report: Where Is Pluripotent Stem Cell Research Now?

The Stem Cell Science Round Up

Human Heart-Forming Organoids – For the first time, researchers have reproduced early human heart development in a culture dish using human pluripotent stem cells.

Bile Duct Organoids Used to Repair Human Livers – A new study has found that when transplanted into damaged mouse or human livers, cholangiocyte organoids functioned normally and repaired bile ducts.

Reversing Severe Muscle Wasting in Disease, Aging, and Trauma – Scientists have discovered a novel protein that triggers muscle stem cells to regenerate, leading to complete muscle replacement and movement in mouse models.

Deletion of Tumor Suppressor Gene Enhances HSC Self-Renewal – Deletions of the Kmt2c gene selectively protect cycling hematopoietic stem cells (HSCs) from differentiation without inducing HSC proliferation themselves.

Photo Reference: Courtesy of Dr. Willy Lensch

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Guest:

Dr. Sean Wu is an Associate Professor of Medicine at the Stanford School of Medicine. The Wu lab seeks to identify mechanisms responsible for human congenital heart disease, and uses mouse models and stem cells to study cardiovascular developmental biology, and to engineer cardiac tissue.

Featured Products and Resources:

• Webinar: Modeling Arrhythmias Using hPSC-Derived Cardiomyocytes and Tracking Their Excitability
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The Stem Cell Science Round Up

hESC-Derived Dopamine Progenitors for Parkinson’s Treatment– Researchers have generated midbrain dopamine neurons from hESCs, and manufactured large-scale cryopreserved dopamine progenitors for clinical use in the treatment of Parkinson’s disease.

Reactivating Neural Crest Pluripotency – A new study suggests that cranial neural crest cells expand their developmental potential through a transient reacquisition of molecular signatures of pluripotency.

Engaging Eosinophils against Liver Injury – Scientists have discovered a mechanism of eosinophil-mediated liver protection that could serve as a therapeutic target to improve outcomes of patients undergoing liver transplantation.

Disrupting the Identity of Heart Muscle Cells – Mutations in the LMNA gene severely disrupt chromatin organization in cardiomyocytes, but not hepatocytes or adipocytes, leading to abnormal activation of non-heart muscle genes.

Photo Reference: Courtesy of Dr. Sean Wu

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Guest:

Dr. Jürgen Knoblich is Scientific Director of the Institute of Molecular Biotechnology at the Austrian Academy of Sciences. The Knoblich lab is known for the development of an organoid model of early brain development, and is currently using iPSCs and cerebral organoids to investigate inter-brain region interactions, neurodevelopmental disorders, and neuronal connections and functions.

Featured Products and Resources:

• Webinar: Challenges in Translating iPSC Technology
• Try the STEMdiff™ Cerebral Organoid Kit

The Stem Cell Science Round Up

Study Reveals Immune Driver of Brain Aging – Researchers have identified a key factor in mental aging, and suggested that it might be prevented or reversed by reprogramming myeloid glucose metabolism.

A Tonsil Organoid System for Studying Adaptive Immunity – Scientists have developed a tonsil organoid system, and used it to evaluate immune responses to rabies and SARS-CoV-2 vaccines.

Antisense Oligonucleotide Targets IRF4 Gene to Treat Multiple Myeloma – Researchers have shown that silencing IRF4 with an antisense oligonucleotide impairs myeloma cell survival and promotes sensitivity to clinical drugs.

Illuminating the Path to Cervical Cancers – By creating novel organoid models, scientists have established a new approach to studying the biology of the cervix, and have identified key turning points in cancer development.

Photo Reference: Courtesy of Dr. Jürgen Knoblich

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