2019 Fiscal Year Final Research Report
Production of mini -pig models exhibiting phenotypes resembling those of human diabetes mellitus and investigation of the effects of islet cell sheets post-transplantation
Project/Area Number |
17K10527
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General surgery
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Research Institution | Meiji University |
Principal Investigator |
Masaki NAGAYA 明治大学, 研究・知財戦略機構(生田), 特任教授 (90329300)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Keywords | 糖尿病 / 膵島移植 / 細胞シート / 細胞凍結 / 細胞移植 / 異種移植 / 鏡視下手術 / 膵島シート |
Outline of Final Research Achievements |
We hypothesized that transplantation of islet cell sheets would be a feasible, safe, and therapeutically effective approach for the treatment of diabetes mellitus (DM). Islet cell sheet was created from transgenic (tg) pigs with a pancreas-specific expression of green fluorescent protein. Besides, we have previously generated transgenic cloned pig models for maturity-onset diabetes of the young type 3 (MODY3). The tg pigs carrying a dominant-negative HNF1α gene developed complications similar to those in human DM patients, such as diabetic retinopathy, cataract, and nodular lesions in the renal glomeruli. However, rearing these pigs is expensive and technically difficult. As the micro-mini pigs handling is easier than that of wild type pigs, gamete intrafallopian transfer (GIFT), a tool of assisted reproductive technology against infertility in humans, was used to produce mini pig models for investigating human DM and the efficacy of islet cell sheet implantation therapy.
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Free Research Field |
一般外科
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Academic Significance and Societal Importance of the Research Achievements |
1型糖尿病患者には、生活の質を改善させるべく膵ランゲルハンス島(膵島)移植療法が行われている。2011年、米国では8000件の心停止ドナーがあったにもかかわらず、僅か1562人の膵臓しか取り出されていない。バーチャル・クロスマッチ陰性の患者が待機リストにいなかったことが主な理由である。膵島が簡便、かつ高品質でバンキングできれば、80%のドナー膵は無駄にならず、細胞の移送もできるなど、移植の柔軟性は高くなる。糖尿病治療の分野においても、膵島シートの研究は進んでいるが、評価できるモデル、移植法も不明である。糖尿病治療の効果を正当に評価できる“モデル”の作出が不可欠である。
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