Clonal expansion of hepatic progenitor cells and differentiation into hepatocyte‐like cells

Hepatic progenitor cells (HPCs) in adult liver are promising for treatment of liver diseases. A biliary‐derived HPC population in adult mice has been characterized by co‐expression of stem cell marker Sry (sex determining region Y)‐box 9 (SOX9) and biliary marker cytokeratin 7 (CK7). However, isolat...

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Bibliographic Details
Published in:	Development, growth & differentiation growth & differentiation, 2019-04, Vol.61 (3), p.203-211
Main Authors:	Liu, Wenbin, Wang, Yujia, Sun, Yufen, Wu, Yingchuan, Ma, Qiwang, Shi, Yun, He, Ruoxu, Zhang, Ting, Ma, Yu, Zuo, Wei, Wu, Zhongjun
Format:	Article
Language:	eng
Subjects:	3D differentiation Cytokeratin Fibroblast growth factor Fibroblast growth factor 9 Fibroblast growth factor receptor 9 Growth factors hepatic progenitor cells Hepatocyte growth factor Hepatocyte nuclear factor 4 isolation and expansion Liver Liver diseases Progenitor cells renal subcapsular transplantation Sox9 protein Stem cells Transforming growth factor-b
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Summary:	Hepatic progenitor cells (HPCs) in adult liver are promising for treatment of liver diseases. A biliary‐derived HPC population in adult mice has been characterized by co‐expression of stem cell marker Sry (sex determining region Y)‐box 9 (SOX9) and biliary marker cytokeratin 7 (CK7). However, isolation of these HPCs in adult healthy liver without any selection procedures remains a big challenge in this field. Here, by establishing a simple and efficient method to isolate and expand the CK7+SOX9+ HPCs in vitro as clones, we acquired a stable and largely scalable cell source. The CK7+SOX9+ progenitor cells were then further induced to differentiate into hepatocyte‐like cells with expression of mature hepatocyte markers albumin (Alb) and hepatocyte nuclear factor 4 alpha (HNF4α), both in vitro and in vivo in the presence of hepatocyte growth factor (HGF) and fibroblast growth factor 9 (FGF9). Furthermore, we found that the HPCs are highly responsive to transforming growth factor‐beta (TGF‐β) signals. Collectively, we identified and harvested a CK7+SOX9+ progenitor cell population from adult mouse liver by a simple and efficient approach. The exploration of this HPC population offers an alternative strategy of generating hepatocyte‐like cells for cell‐based therapies of acute and chronic liver disorders. In this study, without any sorting procedure, CK7+SOX9+HPCs from adult mouse liver were successfully isolated and expanded through a reliable and efficient protocol, provided a promising technique to acquire a plausible cell source for cell therapy of liver disease.
ISSN:	0012-1592 1440-169X