Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats

被引:232
作者
Oyagi, S
Hirose, M
Kojima, M
Okuyama, M
Kawase, M
Nakamura, T
Ohgushi, H
Yagi, K
机构
[1] Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka 5650871, Japan
[2] AIST, RICE, Amagasaki, Hyogo 6610974, Japan
[3] Osaka Univ, Grad Sch Med, Suita, Osaka 5650871, Japan
关键词
bone marrow cells; mesenchymal stem cells; cell therapy; liver injury; autologous transplantation; liver fibrosis;
D O I
10.1016/j.jhep.2005.10.026
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: The autologous transplantation of bone marrow cells is a promising treatment for liver disease. Pluripotent bone marrow stem cells can differentiate into hepatocytes, but few reports address the therapeutic effect of transplanting these stem cells into damaged liver in vivo. Here, we transplanted bone marrow-derived mesenchymal cells (BNMCs) to test their effect in liver-injured rats. Methods: Rat bone marrow cells were cultivated for 2 weeks in the presence or absence of hepatocyte growth factor (HGF), labeled with a fluorescent marker, and transplanted by injection into CCl4-injured rats. Blood samples collected 4 weeks later were analyzed for albumin production and transaminase levels. The amount of fibrosis was determined by histology. Results: RT-PCR analysis detected alpha-fetoprotein and albumin mRNAs in BMMCs cultured with HGF for 2 weeks. Albumin protein was also produced in the BMMC cultures by a subpopulation of cells. Transplantation of the BMMCs into liver-injured rats restored their serum albumin level and significantly suppressed transaminase activity and liver fibrosis. These effects were not seen when the BMMCs were cultured without HGF. Conclusions: The transplantation of BMMCs cultured with HGF effectively treats liver injury in rats. This is a promising technique for autologous transplantation in humans with liver injury. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:742 / 748
页数:7
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