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Clonal expansion of hepatic progenitor cells and differentiation into hepatocyte‐like cells
Author(s) -
Liu Wenbin,
Wang Yujia,
Sun Yufen,
Wu Yingchuan,
Ma Qiwang,
Shi Yun,
He Ruoxu,
Zhang Ting,
Ma Yu,
Zuo Wei,
Wu Zhongjun
Publication year - 2019
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/dgd.12596
Subject(s) - progenitor cell , hepatocyte growth factor , hepatocyte , biology , population , liver regeneration , stem cell , microbiology and biotechnology , cancer research , immunology , in vitro , medicine , regeneration (biology) , genetics , receptor , environmental health
Hepatic progenitor cells ( HPC s) 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 ( SOX 9) and biliary marker cytokeratin 7 ( CK 7). However, isolation of these HPC s 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 CK 7 + SOX 9 + HPC s in vitro as clones, we acquired a stable and largely scalable cell source. The CK 7 + SOX 9 + 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 ( HNF 4α), both in vitro and in vivo in the presence of hepatocyte growth factor ( HGF ) and fibroblast growth factor 9 ( FGF 9). Furthermore, we found that the HPC s are highly responsive to transforming growth factor‐beta ( TGF ‐β) signals. Collectively, we identified and harvested a CK 7 + SOX 9 + 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.