2020 Fiscal Year Final Research Report
Development of oral therapy towards type 1 diabetes and molecular mechanism of cell fate conversion in gut epithelium
| Project/Area Number |
18K19591
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
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| Research Institution | Tokyo Medical and Dental University (2020)
Juntendo University (2018) |
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Principal Investigator |
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Keywords | 分化転換 / 糖尿病 / 再生医学 |
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| Outline of Final Research Achievements |
Clinical trials toward type 1 diabetes are in the process of developing human pancreatic beta cells from iPS/ES cells (2014 Cell, Nat.Biotech) and porcine islets (2016 EBioMed) capsulated by devices. It remains, however, there are the risk of carcinogenesis, avoiding graft rejection and higher cost. The purpose of this study is to develop a novel technology of in vivo direct conversion of somatic cells in digestive tissues instead of on-going gene or cell therapies. As a result of the introduction of reprogramming factors we have identified in Ins-DsRed2 mice expressing DsRed2 under the control of insulin promoter, we found that functional DsRed2-positive insulin-producing cells gave rise to liver and gut epithelial cell in mice by direct conversion. Therefore, it is thought that our technology might be possible to cure T1D patients invasively as easier and safer advantages.
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| Free Research Field |
再生医学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、従来のタンパク・遺伝子補充療法とは異なり、生体内で機能性インスリン産生細胞を作出することを可能にするため、次世代型「細胞運命変換」療法、即ち生体リプログラミングによる治療・創薬を提唱するものである。従って、インスリンの連日投与と血糖管理の負担や膵島移植によるドナー不足や免疫応答による拒絶反応が起こる等、今日の1型糖尿病の治療法が抱える課題を克服する可能性が期待される。更に試験管内で作製した膵β細胞用いた細胞治療(アロ移植・異種細胞移植・自家移植)で抱える安全性・コスト髙・免疫拒絶の問題を改善することが期待されるため、post cell therapyの創薬開発に繋がると考えられる。
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