Ep. 318: “Modeling Reproduction and Endocrinology” Featuring Dr. Kotaro Sasaki

In this episode of The Stem Cell Podcast, hosts Drs. Daylon James and Arun Sharma welcome Dr. Kotaro Sasaki from the University of Pennsylvania School of Veterinary Medicine to discuss his pioneering work in modeling human reproductive and endocrine systems using pluripotent stem cells. Sasaki’s lab focuses on three interconnected areas: in vitro gametogenesis, testicular somatic cell development, and adrenal gland organoid modeling. He details his systematic approach—rooted in developmental biology—to recreate human germ cell development from stem cells, highlighting key discoveries such as the origin of primordial germ cells in the nascent amniotic layer in primates, a major divergence from mouse models. His team has advanced to generating spermatogonia-like cells from human iPSCs and is now tackling the next major hurdle: completing meiosis to produce functional haploid sperm. Simultaneously, Sasaki’s lab has made breakthroughs in modeling the human adrenal gland, successfully recapitulating its zonal architecture in organoids by combining iPSC-derived progenitors with capsule-like cells. These models offer unprecedented tools to study adrenal development, disease, and steroidogenesis. The hosts reflect on the broader implications of this work, from treating infertility and adrenal insufficiency to the ethical and technical challenges of translating in vitro gametogenesis into clinical practice. The episode closes with a powerful call to learn from nature’s blueprint—using developmental biology as a guide—rather than forcing synthetic solutions, underscoring the elegance of recapitulating biological processes step by step. Key takeaways include: (1) In vitro gametogenesis is progressing rapidly, with human germ cell development now being systematically modeled using insights from developmental biology; (2) The adrenal gland’s complex zonation can be reconstituted in vitro using iPSC-derived organoids, enabling new research into endocrine disorders; (3) The success of these models hinges on mimicking in vivo developmental cues, especially the critical role of somatic cells in germ cell maturation; (4) Ethical and safety barriers remain high for clinical application of in vitro-derived gametes, requiring extensive non-human primate testing; (5) The field’s progress is a testament to the power of learning from model organisms and developmental biology before engineering stem cell systems.