近日,第二军医大学胡以平课题组经过4年艰辛攻关,实现了小鼠成纤维细胞向肝干细胞分化的重编程,并证明了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。相关研究在线发表于《细胞—干细胞》上。
肝干细胞是肝脏中数量极少,但可分化产生肝细胞和胆管上皮细胞的“种子细胞”。它所产生的这两种细胞,可以参与肝脏细胞的自然更新和肝脏组织的损伤修复,对肝脏的正常结构和功能的维持具有重要作用。
胡以平课题组联合内蒙古大学以及中科院上海生科院生物化学与细胞生物学研究所、动物研究所和健康科学研究所等单位的科学家,在国家重大科学研究计划等项目的支持下,采用细胞重编程的研究策略,从参与肝脏器官发生和肝干细胞干性维持的调控因子中,筛选到两个可以高效将小鼠成纤维细胞转化为肝干细胞的调控因子,由此建立了在实验室里制备肝干细胞的技术体系。
同时,研究人员证明,采用这种体系所产生的肝干细胞可以在实验室里大量扩增,并具有参与损伤肝脏修复的功能。
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等奠定了新基础。
目前,胡以平课题组正致力于该成果的临床转化研究。该团队成员何志颖表示,如果这一转化获得成功,临床上缺乏有效治疗方法的各种肝脏疾病(包括各种原因所致的末期肝病),就可以利用患者自身的细胞来制备肝干细胞,然后将这种肝干细胞移植回患者体内,以实现临床治疗的目的。(生物谷 Bioon.com)
生物谷推荐的英文摘要
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.