汉氏联合集团

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肝病治疗再获突破性进展

2016-11-072727点击

2013年7月18日《细胞—干细胞》在线刊登了上海第二军医大学胡以平教授团队的最新科研成果，该课题组经过4年攻关，实现了小鼠成纤维细胞向肝干细胞分化的重编程，并证明通过这种重编程方法所产生的肝干细胞具有与活体内自然存在的肝干细胞相似的生物学特性。

这在中国的肝干细胞研究上是一个重大突破。研究人员发现仅用 Hnf1β and Foxa3 两种调控因子就足以将小鼠的胚胎成纤维细胞转化为肝干细胞，从而建立了在实验室里制备肝干细胞的技术体系。这些肝干细胞能在实验室中扩增，并修复受损肝脏。在胡以平教授看来，各种肝病，包括晚期肝病，都能用病人自己的细胞制成的肝干细胞治愈，不过关键首先要在临床上取得进展。这一成果的问世，为人类肝脏疾病的细胞治疗、新药开发以及组织工程研究奠定了新基础。

原文检索：

1. Cell stem cell

Reprogramming Fibroblasts into Bipotential Hepatic Stem Cells by Defined Factors

Recent studies have demonstrated direct reprogramming of fibroblasts into a range of somatic cell types, but to date stem or progenitor cells have only been reprogrammed for the blood and neuronal lineages. We previously reported generation of induced hepatocyte-like (iHep) cells by transduction of Gata4, Hnf1α, and Foxa3 in p19 Arf null mouse embryonic fibroblasts (MEFs). Here, we show that Hnf1β and Foxa3, liver organogenesis transcription factors, are sufficient to reprogram MEFs into induced hepatic stem cells (iHepSCs). iHepSCs can be stably expanded in vitro and possess the potential of bidirectional differentiation into both hepatocytic and cholangiocytic lineages. In the injured liver of fumarylacetoacetate hydrolase (Fah)-deficient mice, repopulating iHepSCs become hepatocyte-like cells. They also engraft as cholangiocytes into bile ducts of mice with DDC-induced bile ductular injury. Lineage conversion into bipotential expandable iHepSCs provides a strategy to enable efficient derivation of both hepatocytes and cholangiocytes for use in disease modeling and tissue engineering.

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