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Transdifferentiation of bone marrow-derived cells into hepatic lineage cells: the methods of transdifferentiation in vitro and hepatic cells transplantation in vivo

骨髓来源细胞转分化为肝谱系细胞：体外转分化和体内肝细胞移植的方法

基本信息

批准号：
14570467
负责人：
KISO Shinichi
金额：
$ 2.05万
依托单位：
OSAKA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

Evidence that bone marrow cells have trans-differencing potential to hepatocytes have been described in recent reports. However, the molecular mechanism underlying this phenomenon is unclear. To address this issue, we investigated the parameters involved in the trans-differentiation ob bone marrow cells into hepatic lineage. (Methods) Mouse BM cells were cultured in a collagen gel without or with growth factors, including basic fibroblast growth factor. The expression of hepatocyte-specific markers, cholangiocyte-specific marker and liver-enriched transcription factors was identified by RT-PCR and immunohistochemistry. (Results) Basic fibroblast growth factor was found to be the most effective for inducing albumin in cultured BM cells. Furthermore, on stimulation of basic fibroblast growth factor, BM cells were found to express other hepatocyte-specific markers and a cholangiocyte-specific marker. This conversion was found to be associated with the induction of transcription factors including hepatocyte nuclear factors and GATA family proteins. (Conclusion) We established an in vitro culture system in which mouse bone marrow cells could trans-differentiate to hepatic lineage cells in response to growth factors. In particular, basic fibroblast growth factor has the ability to induce the trans-differentiation into hepatic lineage cells from BM cells.

最近的报告描述了骨髓细胞具有向肝细胞转分化潜力的证据。然而，这种现象背后的分子机制尚不清楚。为了解决这个问题，我们研究了骨髓细胞转分化为肝谱系所涉及的参数。 (方法)将小鼠BM细胞在不含或含有生长因子（包括碱性成纤维细胞生长因子）的胶原凝胶中培养。通过RT-PCR和免疫组化鉴定肝细胞特异性标记物、胆管细胞特异性标记物和肝脏富集转录因子的表达。（结果）发现碱性成纤维细胞生长因子对于在培养的 BM 细胞中诱导白蛋白最有效。此外，在碱性成纤维细胞生长因子的刺激下，发现BM细胞表达其他肝细胞特异性标记物和胆管细胞特异性标记物。研究发现这种转化与转录因子（包括肝细胞核因子和 GATA 家族蛋白）的诱导有关。（结论）我们建立了一种体外培养系统，其中小鼠骨髓细胞可以响应生长因子转分化为肝谱系细胞。特别是，碱性成纤维细胞生长因子具有诱导BM细胞转分化为肝谱系细胞的能力。

项目成果

期刊论文数量（48）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Y.Kamada, S.Tamura(2番目), S.Kiso(3番目), K.Fukui(7番目), (他12名): "Enhanced carbon tetrachroride-induced liver fibrosis in mice lacking adiponectin."Gastroenterology. 125. 1796-1807 (2003)

Y.Kamada、S.Tamura（第 2 位）、S.Kiso（第 3 位）、K.Fukui（第 7 位）（其他 12 名）：“缺乏脂联素的小鼠中四氯化碳诱导的肝纤维化增强。”胃肠病学 125。1796- 1807 (2003)

DOI：
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期刊：
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作者：
通讯作者：

Yoshihiro Kamada, Shinji Tamura, Shinichi Kiso, Hitoshi Matsumoto, Yukiko Saji, Yuichi Yoshida, Koji Fukui, Norikazu Maeda, Hitoshi Nishizawa, Hiroyuki Nagaretanl, Yoshihiro Okamoto, Shinji Kihara, Jun-ichiro Miyagawa, Yasuhisa Shinomura, Tohru Funahashi,

Yoshihiro Kamada、Shinji Tamura、Shinichi Kiso、Hitoshi Matsumoto、Yukiko Saji、Yuichi Yoshida、Koji Fukui、Norikazu Maeda、Hitoshi Nishizawa、Hiroyuki Nagaretanl、Yoshihiro Okamoto、Shinji Kihara、Jun-ichiro Miyakawa、Ysuhisa Shinomura、Tohru Funahashi、