Ep. 284: “Organ Chip Engineering” Featuring Dr. Milica Radisic
Dec 10, 2024
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Dr. Milica Radisic, a Professor at the University of Toronto and Canada Research Chair, dives into the innovative realm of organ chip engineering. She shares the exciting challenges of maturing cardiomyocytes using macrophages to improve cardiac tissue function. Milica discusses the sustainability issues with microfluidic chips and how her lab's models are reducing reliance on lab animals. As a burgeoning entrepreneur, she reflects on her journey and the landscape for women in business, offering valuable insights from her mentor, Dr. Bob Langer.
Dr. Milica Radisic discusses the innovative use of organ-on-a-chip engineering to replicate human organ functions for disease modeling and drug discovery.
The podcast highlights the significant advancements in developing expandable human fetal pancreas organoids, which can produce all major pancreatic cell types for disease research.
Insights into hematopoietic stem cell dynamics reveal how developmental stages impact blood cell production and imply significant implications for age-related disorders.
Deep dives
Organ Chip Engineering and Its Applications
The discussion revolves around organ chip engineering, specifically focusing on the development of organ-on-a-chip systems that model human physiology and disease. This technology aims to replicate essential organ functions, especially cardiac tissue, using human cells derived from induced pluripotent stem cells (iPSCs). The use of iPSCs allows researchers to create patient-specific models that can closely mimic real tissue behavior and responses to drugs or diseases, ultimately improving drug discovery processes. These organ chips hold promise for progressively addressing unmet needs in regenerative medicine and personalized healthcare.
Recent Advances in Pancreatic Organoids
Recent research highlights significant advancements in creating expandable, long-term human fetal pancreas organoids capable of generating all three major pancreatic cell lineages: acinar, ductal, and endocrine cells. This breakthrough offers a comprehensive model to study pancreatic development and disease, particularly in understanding diabetes. Researchers established 18 distinct organoid lines sourced from early gestational samples, demonstrating remarkable reproducibility and stability over extended culture periods. The ability to derive distinct pancreatic cell types from a single organoid has critical implications for disease modeling and therapeutic development.
The Role of Fetal Stem Cells in Hematopoiesis
A comprehensive analysis of hematopoietic stem and progenitor cell dynamics reveals how developmental stages influence blood cell production. The study integrates single-cell sequencing approaches across different ages, demonstrating that fetal hematopoietic stem cells possess a higher self-renewal capacity compared to their adult counterparts. This research points to significant implications for understanding age-related blood disorders and the variances in response to treatments. Validating fetal stem cell profiles concerning acute myeloid leukemia showcases a unique relationship between early hematopoietic conditions and cancer prognosis.
Mechanotransduction in Intestinal Stem Cells
New insights into intestinal stem cells emphasize the importance of mechanotransduction via piezo channels in regulating cellular behavior within their niche. Studies confirm that the absence of these channels leads to rapid lethality in model organisms, thus highlighting their critical role in maintaining stem cell function in the intestine. By applying in vivo genetic models and single-cell transcriptomics, researchers have demonstrated how mechanical signals from the intestinal microenvironment shape stem cell differentiation and maintenance. This understanding lays the groundwork for future therapeutic strategies targeting intestinal health and regeneration.
The Intersection of Aging and Cancer Risk
Emerging research examines the paradox of increasing cancer incidence in aging populations while noting a decline in cancer cases beyond the age of 80. Findings suggest that the accumulation of somatic mutations in adult stem cells contributes to a heightened risk of cancers such as lung adenocarcinoma. Investigations reveal a crucial relationship between iron deficiency and the loss of stemness in aged epithelial cells, indicating a potential avenue for therapeutic intervention. This interplay between age, stem cell fitness, and cancer susceptibility highlights the complexity of cancer biology, necessitating renewed focus on early diagnostic strategies and preventive measures in younger patients.
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.
