title: Generation of polyhormonal and multipotent pancreatic progenitor lineages from human pluripotent stem cells.
abstract: Generation of pancreatic β-cells from human pluripotent stem cells (hPSCs) has enormous importance in type 1 diabetes (T1D), as it is fundamental to a treatment strategy based on cellular therapeutics. Being able to generate β-cells, as well as other mature pancreatic cells, from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) will also enable the development of platforms that can be used for disease modeling and drug testing for a variety of pancreas-associated diseases, including cystic fibrosis. For this to occur, it is crucial to develop differentiation strategies that are robust and reproducible across cell lines and laboratories. In this article we describe two serum-free differentiation protocols designed to generate specific pancreatic lineages from hPSCs. Our approach employs a variety of cytokines and small molecules to mimic developmental pathways active during pancreatic organogenesis and allows for the in vitro generation of distinct pancreatic populations. The first protocol is designed to give rise to polyhormonal cells that have the potential to differentiate into glucagon-producing cells. The second protocol is geared to generate multipotent pancreatic progenitor cells, which harbor the potential to generate all pancreatic lineages including: monohormonal endocrine cells, acinar, and ductal cells.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; McEwen Centre for Regenerative Medicine, Toronto, ON M5G 1L7, Canada; Toronto General Research Institute, Department of Experimental Therapeutics, University Health Network, Toronto, ON M5G 1L7, Canada.
authors.forename: Roman
authors.initials: R
authors.lastname: Korytnikov
authors.affiliation: Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; McEwen Centre for Regenerative Medicine, Toronto, ON M5G 1L7, Canada; Toronto General Research Institute, Department of Experimental Therapeutics, University Health Network, Toronto, ON M5G 1L7, Canada. Electronic address: cnostro@uhnresearch.ca.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Nostro
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D003470:Culture Media; D005260:Female; D000066449:Human Embryonic Stem Cells / Q000502:physiology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology / Q000637:transplantation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID
chemical_list: D003470:Culture Media
keywords: Beta cells; Diabetes; Differentiation; Human embryonic stem cells (hESCs); Human induced pluripotent stem cells (hiPSCs); Pancreas