近日,，第二軍醫(yī)大學(xué)胡以平課題組經(jīng)過4年艱辛攻關(guān),，實(shí)現(xiàn)了小鼠成纖維細(xì)胞向肝干細(xì)胞分化的重編程，并證明了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,。相關(guān)研究在線發(fā)表于《細(xì)胞—干細(xì)胞》上,。
肝干細(xì)胞是肝臟中數(shù)量極少，但可分化產(chǎn)生肝細(xì)胞和膽管上皮細(xì)胞的“種子細(xì)胞”,。它所產(chǎn)生的這兩種細(xì)胞,，可以參與肝臟細(xì)胞的自然更新和肝臟組織的損傷修復(fù)，對(duì)肝臟的正常結(jié)構(gòu)和功能的維持具有重要作用,。
胡以平課題組聯(lián)合內(nèi)蒙古大學(xué)以及中科院上海生科院生物化學(xué)與細(xì)胞生物學(xué)研究所,、動(dòng)物研究所和健康科學(xué)研究所等單位的科學(xué)家，在國(guó)家重大科學(xué)研究計(jì)劃等項(xiàng)目的支持下,，采用細(xì)胞重編程的研究策略,，從參與肝臟器官發(fā)生和肝干細(xì)胞干性維持的調(diào)控因子中，篩選到兩個(gè)可以高效將小鼠成纖維細(xì)胞轉(zhuǎn)化為肝干細(xì)胞的調(diào)控因子,，由此建立了在實(shí)驗(yàn)室里制備肝干細(xì)胞的技術(shù)體系,。
同時(shí)，研究人員證明,，采用這種體系所產(chǎn)生的肝干細(xì)胞可以在實(shí)驗(yàn)室里大量擴(kuò)增,，并具有參與損傷肝臟修復(fù)的功能。
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)以及組織工程研究等奠定了新基礎(chǔ),。
目前，胡以平課題組正致力于該成果的臨床轉(zhuǎn)化研究,。該團(tuán)隊(duì)成員何志穎表示,，如果這一轉(zhuǎn)化獲得成功，臨床上缺乏有效治療方法的各種肝臟疾?。òǜ鞣N原因所致的末期肝?。涂梢岳没颊咦陨淼募?xì)胞來制備肝干細(xì)胞,，然后將這種肝干細(xì)胞移植回患者體內(nèi),，以實(shí)現(xiàn)臨床治療的目的。（生物谷 Bioon.com）
生物谷推薦的英文摘要
Cell stem cell doi：10.1016/j.stem.2013.06.017
Reprogramming Fibroblasts into Bipotential Hepatic Stem Cells by Defined Factors
Bing Yu1, 2, 11, Zhi-Ying He1, 2, 11, Pu You1, 2, 10, Qing-Wang Han1, 2, Dao Xiang1, 2, Fei Chen1, 2, Min-Jun Wang1, 2, Chang-Cheng Liu1, 2, Xi-Wen Lin3, Uyunbilig Borjigin4, Xiao-Yuan Zi1, 2, Jian-Xiu Li1, 2, Hai-Ying Zhu1, 2, Wen-Lin Li1, 2, Chun-Sheng Han3, Kirk J. Wangensteen5, Yufang Shi6, 7, Li-Jian Hui8, Xin Wang4, 8, 9, , , Yi-Ping Hu1, 2
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.
