2017 Fiscal Year Final Research Report
Bioinformatics approach to establish preconditioning method for beta cell replacement
| Project/Area Number |
15K10033
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 膵島移植 / 細胞移植 / 糖尿病 / 再生医療 / 免疫寛容 |
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| Outline of Final Research Achievements |
Strategies to reduce the immunogenicity of pancreatic islets is essential for successful islet engraftment. We previously demonstrated that mitomycin C (MMC) pretreatment significantly prolonged graft survival. Fully understanding the biological process could result in the development of a protocol. The gene expression analysis identified downregulation of annotated functions associated with cellular movement and revealed significant downregulation of multiple genes encoding proinflammatory mediators with chemotactic activity. Validation studies revealed significantly decreased levels of IL-6, MCP-3, and MMP-2 in culture supernatants of MMC-treated islets. We also showed that MMC-treated islets secreted lower levels of chemoattractants that synergistically reduced the immunogenic potential of islets. The pretreatment of islets with MMC can reduce the immunogenic potential and prolong the survival of islet grafts by inducing the suppression of multiple leukocyte chemotactic factors.
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| Free Research Field |
外科学
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