2005 Fiscal Year Final Research Report Summary
β-cell neogenesis induced by adenovirus-mediated gene delivery into mice pancreas
| Project/Area Number |
16590881
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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 |
Metabolomics
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| Research Institution | Osaka University |
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Principal Investigator |
TASHIRO Fumi Osaka University, Graduate School of Medicine, Instructor, 医学系研究科, 助手 (40136213)
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| Project Period (FY) |
2004 – 2005
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| Keywords | diabetes / gene / adenoviral vector / regenerative medicine |
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| Research Abstract |
Transplantation of pancreas or pancreatic islets is a potential therapeutic approach for diabetes. However, its clinical application has several limitations, including immunological rejection and insufficient availability of β cells for transplantation. The latest attention has focused on the possible therapeutic use of the controlled differentiation of adult pancreatic stem cells into insulin producing cells. We have reported that delivering the pancreatic transcription factor gene, pdx-1, to mouse pancreas by adenoviral vector resulted in β cell neogensis and ductal proliferation. But the number of insulin producing cells was not sufficient to cure diabetes, so that we investigated other factors promoting β cells neogenesis in this study.
The area of ductal proliferation generated after delivery of adenoviral vector was investigated by immunohistochemical staining. Proliferative duct-like structure was stained with anti-CK19 antibody, a marker of ductal tissue. To improve the efficiency of induction in neogensis of insulin-producing cells, we examined the other transcription factors and growth factors relating pancreatic development. IGF-1 participates in pancreatic development and its signal transmission is mediated by AKT. Introducing of IGF-1 gene with pdx-1 gene using adenoviral vectors resulted in significant increase in ductal proliferation and neogenesis of insulin-producing cells.
Thus, this procedure may be a useful technique for inducing neogenesis of the insulin-producing cells, leading to the regenerative therapy for diabetes mellitus.
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