Ep. 275: “Liver Organogenesis” Featuring Dr. Ludovic Vallier
Sep 3, 2024
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Dr. Ludovic Vallier, a leading expert in stem cells from the Berlin Institute of Health, shares groundbreaking insights into liver organogenesis. He discusses modeling non-alcoholic fatty liver disease and how his lab transitioned to researching SARS-CoV-2 during the pandemic. Vallier explains the potential of induced pluripotent stem cells (iPSCs) for liver regeneration after injury. The conversation also sheds light on the innovative therapies being developed for liver diseases and the collaboration happening within Germany's scientific community.
Dr. Ludovic Vallier emphasizes the importance of understanding cell fate decisions during liver organogenesis to generate essential liver cell types for therapeutic applications.
The podcast discusses advancements in interspecies chimerism aimed at enhancing human and non-human cell adhesion, potentially aiding organ transplantation efforts.
Innovative iPSC models are being utilized to uncover glial cell roles in Multiple Sclerosis, identifying new therapeutic targets for this debilitating disease.
Deep dives
Liver Organogenesis and Research Focus
The research focuses on liver organogenesis and the cellular dynamics involved in liver development and regeneration. Dr. Ludovic Vallier emphasizes the relevance of understanding cell fate choices during liver organogenesis to generate functional cell types essential for liver health, such as hepatocytes and cholangiocytes. His lab aims to address liver diseases, particularly non-alcoholic fatty liver disease, and develop cell-based therapies as potential treatments. By utilizing pluripotent stem cells and organoid technology, the research targets both the fundamental aspects of liver biology and their translational applications in regenerative medicine.
Advances in Interspecies Chimerism
Recent findings have shed light on the challenges facing interspecies chimerism, particularly regarding cell-cell adhesion between human and non-human pluripotent stem cells. Research led by Jun Wu reveals that human cells struggle to adhere to their non-human counterparts due to significant evolutionary barriers. By employing synthetic biology techniques, researchers developed strategies to enhance cell adhesion, successfully increasing chimerism rates in vitro and in vivo. These advances are seen as pivotal steps toward growing human organs in non-human species, potentially alleviating organ shortages for transplantation.
Pathological Insights from Single-Cell Analysis
Innovative approaches in analyzing neurodegenerative diseases, particularly Alzheimer's, employ single-cell RNA sequencing to understand changes in brain health across diverse individual cases. A multi-center study mapped a comprehensive cellular atlas of the prefrontal cortex, revealing distinct cell type changes associated with Alzheimer's and normal aging. By identifying specific glial and neuronal populations linked to cognitive decline, researchers are striving to distinguish between typical aging processes and pathological conditions. This research highlights the importance of appreciating the complexity within multicellular communities in the progression of neurodegenerative diseases.
Patient-Derived Models in Multiple Sclerosis
Research leveraging patient-induced pluripotent stem cell (iPSC) models offers crucial insights into glial cell contributions in Multiple Sclerosis (MS). By developing a broad array of iPSC lines from MS patients, scientists have been able to study intrinsic glial cell dysfunction, revealing key characteristics that differentiate MS-affected cultures from healthy controls. Notably, oligodendrocytes and astrocytes derived from MS patients exhibited increased expression of inflammatory genes, aligning with findings from postmortem brain samples. This model holds potential for identifying new therapeutic targets that specifically address the glial components of this debilitating disease.
Applications of Organoids in Disease Modeling
Organoids represent a transformative tool in modeling various diseases, including the recent advancements in creating brain organoids that replicate specific anatomical structures, such as the spinal trigeminal nucleus. These organoids facilitate the study of neural development, signaling, and pathological mechanisms by allowing researchers to observe cellular interactions in a 3D environment. The integration of diverse cell types within these models enhances the accuracy of disease representation and can lead to novel insights into brain disorders. Consequently, organoid technology has become instrumental in advancing our understanding of cellular behaviors and interactions that drive disease progression.
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.
Glial Cells in Multiple Sclerosis – iPSC-derived multiple sclerosis models provide a unique platform for dissecting glial contributions to disease phenotypes.
