2005 Fiscal Year Final Research Report Summary
Development of therapeutic transplantation of human bone marrow mesenchymal cells into injured liver.
| Project/Area Number |
16590593
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | OSAKA UNIVERSITY |
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Principal Investigator |
KISO Shinichi Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (40335352)
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| Co-Investigator(Kenkyū-buntansha) |
TAMURA Shinji Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (30243223)
SHINOMURA Yasuhisa Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (90162619)
IGURA Takumi Osaka University, Graduate School of Medicine, Endowed Chair Instructor, 医学系研究科, 寄附講座助手 (70403178)
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| Project Period (FY) |
2004 – 2005
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| Keywords | hepatocyte / bone marrow cells / trans-differentiation / cell transplantation / bFGF / regenerative medicine / 骨髄細胞 |
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| Research Abstract |
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 effects of transplanting these stem cells into damaged liver in vivo.
We previously reported that in vitro culture system was established, in which mouse bone marrow cells were trans-differentiated into hepatic lineage cells in response to growth factor stimulation. This conversion of BM cells to hepatic lineage cells is thought to be the tran-differentiation without fusion, because bone marrow cells were not co-cultured with hepatocytes in this study. It is noteworthy that fibroblast growth factors have the ability to induce the transdifferentiation of BM cells into hepatic lineage cells. This conversion is associated with the induction of transcription factors including hepatocyte nuclear factors and the GATA family of proteins.
Specific cell ablation is a useful method for analyzing the in vivo function of cells. We have developed a simple and sensitive method for conditional cell ablation in transgenic mice, called "toxin receptor-mediated cell knockout." We expressed the diphtheria toxin (DT) receptor in transgenic mice using a hepatocyte-specific promoter and found that injection of DT caused fulminant hepatitis. We could transplant mature hepatocytes, obtained from GFP-transgenic mice, into these DT transgenic mice. Transplanting various kinds of stem cells or progenitor cells from GFP-transgenic mice into toxin-sensitive transgenic mice should allow one to follow the development of regenerated cells administration of DT.
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