title: Self-renewing endodermal progenitor lines generated from human pluripotent stem cells.
abstract: The use of human pluripotent stem cells for laboratory studies and cell-based therapies is hampered by their tumor-forming potential and limited ability to generate pure populations of differentiated cell types in vitro. To address these issues, we established endodermal progenitor (EP) cell lines from human embryonic and induced pluripotent stem cells. Optimized growth conditions were established that allow near unlimited (>10(16)) EP cell self-renewal in which they display a morphology and gene expression pattern characteristic of definitive endoderm. Upon manipulation of their culture conditions in vitro or transplantation into mice, clonally derived EP cells differentiate into numerous endodermal lineages, including monohormonal glucose-responsive pancreatic β-cells, hepatocytes, and intestinal epithelia. Importantly, EP cells are nontumorigenic in vivo. Thus, EP cells represent a powerful tool to study endoderm specification and offer a potentially safe source of endodermal-derived tissues for transplantation therapies.
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, PA 19104, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.forename: Lei
authors.initials: L
authors.lastname: Ying
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Aline M
authors.initials: AM
authors.lastname: Galvão
authors.forename: Jason A
authors.initials: JA
authors.lastname: Mills
authors.forename: Henry C
authors.initials: HC
authors.lastname: Lin
authors.forename: Darrell N
authors.initials: DN
authors.lastname: Kotton
authors.forename: Steven S
authors.initials: SS
authors.lastname: Shen
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Nostro
authors.forename: John Kim
authors.initials: JK
authors.lastname: Choi
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Weiss
authors.forename: Deborah L
authors.initials: DL
authors.lastname: French
authors.forename: Paul
authors.initials: P
authors.lastname: Gadue
mesh_terms: D000818:Animals; D002460:Cell Line / Q000166:cytology* / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology* / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous