Hepatic differentiation of human bone marrow-derived mesenchymal stem cells by tetracycline-regulated hepatocyte nuclear factor 3β

被引：78

作者：

Ishii, Kyoko ^{[1
]}

Yoshida, Yoko ^{[2
]}

Akechi, Yuji ^{[1
]}

Sakabe, Tomohiko ^{[1
]}

Nishio, Ren ^{[1
]}

Ikeda, Remina ^{[1
]}

Terabayashi, Kei ^{[1
]}

Matsumi, Yoshiaki ^{[1
]}

Gonda, Kazue ^{[1
]}

Okamoto, Hideharu ^{[3
]}

Takubo, Kazuko ^{[3
]}

Tajima, Fumihito ^{[1
]}

Tsuchiya, Hiroyuki ^{[1
]}

Hoshikawa, Yoshiko ^{[1
]}

Kurimasa, Akihiro ^{[1
]}

Umezawa, Akihiro ^{[4
]}

Shiota, Goshi ^{[1
]}

机构：

[1] Tottori Univ, Grad Sch Med, Div Mol & Genet Med, Dept Genet Med & Regenerat Therapeut, Yonago, Tottori 6838504, Japan

[2] Tokyo Metropolitan Univ, Dept Chem, Grad Sch Sci & Engn, Tokyo 158, Japan

[3] Tottori Univ, Fac Med, Div Oral & Maxillofacial Biopathol Surg, Dept Med Sensory & Motor Organs, Yonago, Tottori 6838504, Japan

[4] Natl Res Inst Child Hlth & Dev, Dept Reprod Biol & Pathol, Tokyo, Japan

来源：

HEPATOLOGY | 2008年 / 48卷 / 02期

关键词：

D O I：

10.1002/hep.22362

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Human bone marrow-derived mesenchymal stem cells (BM-MSCs) are expected to be a potential source of cells for transplantation. Although recent reports have shown that isolated MSCs can differentiate into hepatocytes, the efficiency of differentiation is insufficient for therapeutic application. To circumvent this problem, it is necessary to understand the mechanisms of hepatic differentiation of human BM-MSCs. Hepatocyte nuclear factor 3 beta (HNF3 beta), a forkhead/winged helix transcription factor, is essential for liver development. In the present study, we established a tetracycline (Tet)-regulated expression system for HNF3 beta in UE7T-13 BM-MSCs. HNF3 beta expression significantly enhanced expression of albumin, alpha-fetoprotein (AFP), tyrosine amino transferase (TAT) and epithelial cell adhesion molecule (EpCAM) genes. The differentiated cells showed hepatocyte-specific functions including glycogen production and urea secretion. During treatment with the Tet-on system for 8 days, over 80% of UE7T-13 cells turned out to express albumin. Furthermore, the combination of Tet with basic fibroblast growth factor (bFGF) efficiently induced the genes such as albumin and TAT, which are associated with maturity of hepatocytes; however, it suppressed genes such as AFP and EpCAM, which are associated with immaturity of hepatocytes, suggesting that Tct-induced HNF3 beta expression sensitizes BM-MSCs to bFGF signals. Finally, the results of the present study suggest that down-regulation of Wnt/beta-catenin signals caused by translocation of beta-catenin to cytoplasmic membrane is associated with hepatic differentiation of human BM-MSCs. Conclusion: HNF3 beta expression induced efficient differentiation of UE7T-13 human BM-NISCs.

引用

页码：597 / 606

页数：10

共 26 条

[1] HNF-3-BETA IS ESSENTIAL FOR NODE AND NOTOCHORD FORMATION IN MOUSE DEVELOPMENT [J].