The Liver Meeting 2022-Hans Popper State-of-the-Art Lecture

Video Transcription

Video Summary

Dr. Takenori Takebe, an Associate Professor of Pediatrics and the Endowed Chair of Organoid Medicine at Cincinnati Children's Hospital, gave a lecture on how human liver organoids can be used for drug development. Organoids are 3D tissue structures made from human stem cells that mimic the structure and function of organs, allowing for the study of organ development and disease progression. Dr. Takebe's research focuses on creating functional human liver organoids in a petri dish to study liver tissue renewal, development, and disease. He has successfully developed liver organoids that mimic the zonal-specific markers and functionalities of the liver, such as bile acid elimination and cytochrome activities. He has also integrated sinusoidal endothelial cells and demonstrated their role in liver-specific functions such as factor VIII synthesis and immune interactions. Furthermore, Dr. Takebe has used liver organoids to study non-alcoholic fatty liver disease (NAFLD) and has identified genetic variants, such as GCKR, that contribute to the development of NAFLD. He has also shown differences in the response to treatment, such as metformin, based on genetic variants. Looking ahead, Dr. Takebe highlighted the need for more complex models that incorporate multiple cell types and system-level crosstalk, as well as the potential for transplantation-coupled organoid-based studies to bridge the gap between in vitro and in vivo models.

Asset Caption

Presented by Dr. Takanori Takebe, MD, Pediatrics, Cincinnati Children's Hospital Medical Center

The goal of this program is to propose integrative pre-clinical research concept for human NAFLD/NASH, combining patients’ and engineered human tissues using emerging technologies such as induced pluripotency, organoids, gene editing and comprehensive genomics. By introducing population-based organoid system, this investigative strategy may open the door to the studies of pleiotropic factors, potentially transforming the future of precision hepatology.

Keywords

Human liver organoids

Drug development

Liver tissue renewal

Non-alcoholic fatty liver disease

Genetic variants

Treatment response

Complex models