2007 Fiscal Year Final Research Report Summary
Molecular analysis of differentiation mechanism of hMSC into hepatocyte and application to liver regeneration therapy
| Project/Area Number |
18590740
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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 | Sapporo Medical University |
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Principal Investigator |
TAKIMOTO Rishu Sapporo Medical University, 4th Department of Internal Medicine, Assistant Prof. (10336399)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAYAMA Tetsuji University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, Prof. (10284994)
SATO Yasushi Sapporo Medical University, 4th Department of Internal Medicine, Assistant Prof. (80343383)
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| Project Period (FY) |
2006 – 2007
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| Keywords | hMSC / liver / transdifferentiation |
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| Research Abstract |
Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. We have recently disclosed that human mesenchymal stem cells (MSCs) could transdifferentiate into hepatocyte-like cells when directly xenografting to allylalcohol (AA)-treated rat liver (Blood 2005, 106 : 756-763). However, the efficacy of differentiation into hepatocyte-like cells was at most 0.5% of hMSC injected to rat liver. In this study, we established the immortalized hMSC transduced with hTERT gene as well as Bmi-1 in order to obtain efficient proliferation rate for large-scale preparation. As a result, hMSC-TERT-Bmi-1 clone transdifferentiated into hepatocyte-like cells which produced human albumin and P450, CYP3A4, CYP2C8 and CYP2C9. Furthermore, hepatocyte-like cells derived from hMSC-TERT-Bmi-1 clone could store glycogen and LDL, suggesting that these cells could be applied for drug metabolism, drug sensitivity and virus infection model.
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