Stem cells and advanced tissue engineering for regenerative medicine
2021年1月25日〜1月28日WEB
Stem cells and advanced tissue engineering for regenerative medicine
2021年1月25日〜1月28日WEB
[8]Engineering human hepato-biliary-pancreatic organoids from pluripotent stem cells
○Hiroyuki Koike(Assistant Professor, Department of Biochemistry & Molecular Biology, Nippon Medical School)
Education:
2014.3 Ph.D., Graduate School of Medicine, Yokohama City University
Professional Career:
2014.4-2015.11Postdoctoral Fellow, Institute of Stem Cell Biology and Regenerative Medicine, Stanford University
2015.11-2018.2Research Fellow, Division of Gastroenterology, Hepatology and Nutrition and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center
2018.3-2019.3Assistant Professor, Medical Research Institute, Tokyo Medical and Dental University
2019.4-present Assistant Professor, Department of Biochemistry & Molecular Biology, Nippon Medical School
Human organoids are emerging as a valuable resource to investigate human organ development and disease. The applicability of human organoids has been limited, partly due to the oversimplified architecture of the current technology, which generates single-tissue organoids that lack inter-organ structural connections. Thus, engineering organoid systems that incorporate connectivity between neighboring organs is a critical unmet challenge in an evolving organoid field. Here, we describe a protocol for the continuous patterning of hepatic, biliary and pancreatic (HBP) structures from a three-dimensional culture of human pluripotent stem cells (PSCs). After differentiating PSCs into anterior and posterior gut spheroids, the two spheroids are fused together in one well. Subsequently, self-patterning of multi-organ (i.e. HBP) domains occurs within the boundary region of the two spheroids, even in the absence of any extrinsic factors. Long-term culture of HBP structures induces differentiation of the domains into segregated organs complete with developmentally relevant invagination and epithelial branching. This in-a-dish model of human hepato-biliary-pancreatic organogenesis provides a unique platform for studying human development, congenital disorders, drug development, and therapeutic transplantation. More broadly, our approach could potentially be used to establish inter-organ connectivity models for other organ systems derived from stem cell cultures. Program [PDF]