肝病治療再獲突破性進(jìn)展
2013年7月18日《細(xì)胞—干細(xì)胞》在線刊登了上海第二軍醫(yī)大學(xué)胡以平教授團(tuán)隊的最新科研成果， 該課題組經(jīng)過4年攻關(guān)，實現(xiàn)了小鼠成纖維細(xì)胞向肝干細(xì)胞分化的重編程， 并證明通過這種重編程方法所產(chǎn)生的肝干細(xì)胞具有與活體內(nèi)自然存在的肝干細(xì)胞相似的生物學(xué)特性。
這在中國的肝干細(xì)胞研究上是一個重大突破。研究人員發(fā)現(xiàn)僅用 Hnf1β and Foxa3 兩種調(diào)控因子就足以將小鼠的胚胎成纖維細(xì)胞轉(zhuǎn)化為肝干細(xì)胞，從而建立了在實驗室里制備肝干細(xì)胞的技術(shù)體系。這些肝干細(xì)胞能在實驗室中擴(kuò)增，并修復(fù)受損肝臟。在胡以平教授看來，各種肝病，包括晚期肝病，都能用病人自己的細(xì)胞制成的肝干細(xì)胞治愈，不過關(guān)鍵首先要在臨床上取得進(jìn)展。這一成果的問世，為人類肝臟疾病的細(xì)胞治療、新藥開發(fā)以及組織工程研究奠定了新基礎(chǔ)。
原文檢索：
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.
