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本帖最后由 风雨不动 于 2012-4-14 15:18 编辑
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10116.html#/affil-auth
Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factorsAffiliations
- Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy for Sciences, Yueyang Road 320, 200031 Shanghai, China :Zhiying He, Shuyi Ji, Huawang Sun, Changcheng Liu,Xin Wang &Lijian Hui
- Department of Cell Biology, Second Military Medical University, 800 Xiangyin Road, 200433 Shanghai, China: Zhiying He,Dao Xiang,Changcheng Liu &Yiping Hu
- University of Minnesota, Minneapolis: Xin Wang
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Stem Cell Institute, University of Minnesota, Minneapolis, 55455 Minnesota, USA : Xin Wang
Contributions L.H. conceived the project. P.H. performed most of the experiments. S.J. analysed the in vitro functions of iHep cells. H.S. analysed gene expression of iHep cells. L.H., X.W., P.H. and Z.H. designed the experiments for characterizing in vivo functions of iHep cells. P.H., Z.H., D.X., C.L. and Y.H. performed the in vivo experiments. L.H. and P.H. analysed the data. L.H., P.H. and X.W. wrote the manuscript.
The generation of functional hepatocytes independent of donor liver organs is of great therapeutic interest with regard to regenerative medicine and possible cures for liver disease1. Induced hepatic differentiation has been achieved previously using embryonic stem cells or induced pluripotent stem cells2, 3, 4, 5, 6, 7, 8. Particularly, hepatocytes generated from a patient’s own induced pluripotent stem cells could theoretically avoid immunological rejection. However, the induction of hepatocytes from induced pluripotent stem cells is a complicated process that would probably be replaced with the arrival of improved technology. Overexpression of lineage-specific transcription factors directly converts terminally differentiated cells into some other lineages9, 10, 11, 12, including neurons13, cardiomyocytes14 and blood progenitors15; however, it remains unclear whether these lineage-converted cells could repair damaged tissues in vivo. Here we demonstrate the direct induction of functional hepatocyte-like (iHep) cells from mouse tail-tip fibroblasts by transduction of Gata4, Hnf1α and Foxa3, and inactivation of p19Arf. iHep cells show typical epithelial morphology, express hepatic genes and acquire hepatocyte functions. Notably, transplanted iHep cells repopulate the livers of fumarylacetoacetate-hydrolase-deficient (Fah−/−) mice and rescue almost half of recipients from death by restoring liver functions. Our study provides a novel strategy to generate functional hepatocyte-like cells for the purpose of liver engineering and regenerative medicine.
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