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利用二肽基肽酶IV缺陷型突变大鼠证明肝祖细胞的分化

Demonstration of differentiation in hepatocyte progenitor cells using dipeptidyl peptidase IV deficient mutant rats.

作者信息

Sigal S H, Rajvanshi P, Reid L M, Gupta S

机构信息

Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.

出版信息

Cell Mol Biol Res. 1995;41(1):39-47.

PMID:7550451
Abstract

The presence of progenitor or stem cells in the adult liver and their potential roles in oncogenesis are unresolved issues. The study of hepatocyte progenitor cells has been limited by a lack of convenient in vivo systems allowing unequivocal cell localization and demonstration of differentiation into hepatocytes. To develop an in vivo progenitor bioassay, early (E14) fetal Fischer 344 rat hepatoblasts were transplanted into the spleen of syngeneic, weaning rats deficient in dipeptidyl peptidase IV (DPPIV) activity. The donor status of transplanted hepatoblasts was demonstrated by DPPIV expression. Localization of hepatoblasts was facilitated by the use of an ectopic site, as well as weanling recipients, which readily allowed identification of very small numbers of transplanted cells. Fetal rat hepatoblasts were demonstrated to undergo cellular differentiation along the hepatocyte lineage by acquiring glucose-6-phosphatase activity within 5 d of transplantation. A critical review of previous transplantation studies of hepatocyte progenitor cells and the role of the local microenvironment at inducing differentiation indicates that this novel bioassay should facilitate analysis of progenitor cells.

摘要

成体肝脏中祖细胞或干细胞的存在及其在肿瘤发生中的潜在作用仍是未解决的问题。肝细胞祖细胞的研究受到缺乏方便的体内系统的限制,该系统能明确细胞定位并证明其向肝细胞的分化。为了开发一种体内祖细胞生物测定法,将早期(E14)胎鼠Fischer 344大鼠肝母细胞移植到同基因、缺乏二肽基肽酶IV(DPPIV)活性的断奶大鼠的脾脏中。通过DPPIV表达证明移植肝母细胞的供体状态。利用异位位点以及断奶受体有助于肝母细胞的定位,这使得很容易识别极少量的移植细胞。移植后5天内,胎鼠肝母细胞通过获得葡萄糖-6-磷酸酶活性被证明沿肝细胞谱系发生细胞分化。对先前肝细胞祖细胞移植研究以及局部微环境在诱导分化中的作用的批判性综述表明,这种新型生物测定法应有助于祖细胞的分析。

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