Self-Renewing Endodermal Progenitor Lines Generated from Human Pluripotent Stem Cells

被引：200

作者：

Cheng, Xin ^{[1
,2
]}

Ying, Lei ^{[1
,2
]}

Lu, Lin ^{[1
,2
]}

Galvao, Aline M. ^{[1
,2
]}

Mills, Jason A. ^{[1
,2
]}

Lin, Henry C. ^{[4
]}

Kotton, Darrell N. ^{[5
,6
]}

Shen, Steven S. ^{[7
,8
]}

Nostro, M. Cristina ^{[9
]}

Choi, John Kim ^{[1
]}

Weiss, Mitchell J. ^{[3
]}

French, Deborah L. ^{[1
,2
]}

Gadue, Paul ^{[1
,2
]}

机构：

[1] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[2] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA 19104 USA

[3] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA

[4] Childrens Hosp Philadelphia, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA

[5] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA

[6] Boston Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02118 USA

[7] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA

[8] Boston Med Ctr, Boston, MA 02118 USA

[9] Univ Hlth Network, McEwen Ctr Regenerat Med, Toronto, ON M5G 1L7, Canada

来源：

CELL STEM CELL | 2012年 / 10卷 / 04期

关键词：

DEFINITIVE ENDODERM; EFFICIENT DIFFERENTIATION; VISCERAL ENDODERM; GENE-EXPRESSION; ENDOCRINE-CELLS; IPS CELLS; IN-VITRO; MOUSE; INSULIN; GASTRULATION;

D O I：

10.1016/j.stem.2012.02.024

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

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 beta-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.

引用

页码：371 / 384

页数：14

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