生物
祖细胞
祖细胞
体外
移植
肝细胞
体内
癌症研究
细胞生物学
免疫学
再生(生物学)
肝再生
干细胞
遗传学
内科学
医学
作者
Kun Zhang,Ludi Zhang,Wenming Liu,Xiaolong Ma,Jin Cen,Zhen Sun,Chenhua Wang,Sisi Feng,Zhengtao Zhang,Liyun Yue,Hui Lu,Zhenfeng Zhu,Xiaotao Chen,Anqi Feng,Jiaying Wu,Zhiwu Jiang,Peng Li,Xin Cheng,Dong Gao,Luying Peng,Lijian Hui
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2018-12-01
卷期号:23 (6): 806-819.e4
被引量:146
标识
DOI:10.1016/j.stem.2018.10.018
摘要
Transplantation of human hepatocytes (HHs) holds significant potential for treating liver diseases. However, the supply of transplantable HHs is severely constrained by limited donor availability and compromised capacity for in vitro expansion. In response to chronic injury, some HHs are reprogrammed into proliferative cells that express both hepatocyte and progenitor markers, suggesting exploitable strategies for expanding HHs in vitro. Here, we report defined medium conditions that allow 10,000-fold expansion of HHs. These proliferating HHs are bi-phenotypic, partially retaining hepatic features while gaining expression of progenitor-associated genes. Importantly, these cells engraft into injured mouse liver at a level comparable to primary HHs, and they undergo maturation following transplantation in vivo or differentiation in vitro. Thus, this study provides a protocol that enables large-scale expansion of transplantable HHs, which could be further developed for modeling and treating human liver disease.
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