Generation of Functional Hepatocytes From Mouse Induced Pluripotent Stem Cells

被引:34
|
作者
Li, Weiqiang [1 ,2 ]
Wang, Ding [1 ,2 ]
Qin, Jie [1 ,2 ]
Liu, Chang [1 ,2 ]
Zhang, Qi [3 ]
Zhang, Xiuming [1 ,2 ]
Yu, Xinbing [1 ,2 ]
Lahn, Bruce T. [1 ,2 ,4 ,5 ]
Mao, Frank Fuxiang [1 ,2 ,4 ,5 ]
Xiang, Andy Peng [1 ,2 ,6 ,7 ]
机构
[1] Sun Yat Sen Univ, Ctr Stem Cell Biol & Tissue Engn, Guangzhou 510080, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Minist Educ, Key Lab Stem Cells & Tissue Engn, Guangzhou 510080, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Hosp 3, Div Hepatol, Guangzhou 510080, Guangdong, Peoples R China
[4] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA
[5] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA
[6] Sun Yat Sen Univ, Zhongshan Med Sch, Dept Biochem, Guangzhou 510080, Guangdong, Peoples R China
[7] Sun Yat Sen Univ, State Key Lab Ophthalmol, Guangzhou 510080, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
IN-VITRO DIFFERENTIATION; DEFINITIVE ENDODERM; PROGENITOR CELLS; SODIUM-BUTYRATE; LEUKEMIA-CELLS; LIVER; EFFICIENT; PRECURSORS; EXPRESSION; RECEPTORS;
D O I
10.1002/jcp.22000
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Induced pluripotent stem cells are derived from somatic cells by forced expression of several transcriptional factors. Induced pluripotent stem cells resemble embryonic stem cells in many aspects, such as the expression of certain stem cell markers, chromatin methylation patterns, embryoid body formation and teratoma formation. Therefore, induced pluripotent stem cells provide a powerful tool for study of developmental biology and unlimited resources for transplantation therapy. Here we reported the successful induction of mouse induced pluripotent stem cells and a simple and efficient process for generation of functional hepatocytes from mouse induced pluripotent stem cells by sequential addition of inducing factors. These induced pluripotent stem cell-derived hepatocytes, just as mouse embryonic stem cell-derived hepatocytes, expressed hepatic lineage markers including CK7, CK8, CK18, CK19, alpha-fetoprotein, albumin, Cyp7a1, and exhibited functional hepatic characteristics, including glycogen storage, indocyanine green (ICG) uptake and release, low-density lipoprotein (LDL) uptake and urea secretion. Although we observed some variations in the efficiency of hepatic differentiation between induced pluripotent stem cells and common mouse embryonic stem cell lines, our results indicate that mouse induced pluripotent stem cells can efficiently differentiate into functional hepatocytes in vitro, which may be helpful for the study of liver development and regenerative medicine. J. Cell. Physiol. 222: 492-501, 2010. (C) 2009 Wiley-Liss, Inc.
引用
收藏
页码:492 / 501
页数:10
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