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Hepatic differentiation of human bone marrow‐derived UE7T‐13 cells: Effects of cytokines and CCN family gene expression
Author(s) -
Shimomura Takashi,
Yoshida Yoko,
Sakabe Tomohiko,
Ishii Kyoko,
Gonda Kazue,
Murai Rie,
Takubo Kazuko,
Tsuchiya Hiroyuki,
Hoshikawa Yoshiko,
Kurimasa Akihiro,
Hisatome Ichiro,
Uyama Taro,
Umezawa Akihiro,
Shiota Goshi
Publication year - 2007
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2007.00162.x
Subject(s) - hepatocyte growth factor , basic fibroblast growth factor , biology , growth factor , microbiology and biotechnology , cellular differentiation , bone marrow , transdifferentiation , endocrinology , stem cell , immunology , biochemistry , gene , receptor
Aim: Bone marrow‐derived mesenchymal stem cells (MSC) are expected to be an excellent source of cells for transplantation. We aimed to study the culture conditions and involved genes to differentiate MSC into hepatocytes. Methods: The culture conditions to induce the efficient differentiation of human bone marrow‐derived UE7T‐13 cells were examined using cytokines, hormones, 5‐azacytidine and type IV collagen. Results: We found that combination of acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF) with type IV collagen coating induced hepatic differentiation of UE7T‐13 cells at over 30% frequency, where expression of albumin mRNA was increased over 20‐fold. The differentiated cells had functions of albumin production, glycogen synthesis and urea secretion as well as expressing hepatocyte‐specific genes. In addition, these cellshave binuclear and cuboidal morphology, which is a characteristic feature of hepatocytes. During hepatic differentiation, UE7T‐13 cells showed depressed expression of WISP1 and WISP2 genes, members of the CCN family. Conversely, knockdown of WISP1 or WISP2 gene by siRNA stimulated hepatic differentiation. The effect of aFGF/bFGF/HGF/type IV collagen coating and WISP1‐siRNA on hepatic differentiation was additive. Conclusion: The present study suggests that aFGF/bFGF/HGF/type IV collagen coating is the efficient condition for hepatic differentiation of UE7T‐13 cells, and that WISP1 and WISP2 play an important role in hepatic transdifferentiation of these cells.