Differentiation of functional islets from human iPS cells and hiPS-endocrine progenitor cells in vitro.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K21006
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery; Digestive surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Watanabe Ami 東京大学, 定量生命科学研究所, 特任研究員 (40611421)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: iPS / 膵島

Outline of Final Research Achievements

To identify pancreatic endocrine progenitor cell markers, we performed microarray analysis of iPS cell-derived pancreatic endocrine progenitor cells. As a result, we discovered a new cell surface marker CD82 for endocrine progenitor cells. iPS-derived pancreatic progenitor cells were isolated from endocrine progenitor cells and found to efficiently generate cells that secrete insulin. Furthermore, this gene was also expressed in mature pancreatic islets. Marker-positive cells isolated from mature human islets showed a strong ability to secrete insulin and expressed mature beta cell markers such as Ucn3. We also found that suppression of this gene with siRNA inhibited the maturation of insulin-secreting pancreatic beta cells. This study indicates that the expression of this marker gene plays an important role in the maturation of pancreatic endocrine cells, especially pancreatic beta cells, and provides new insights into understanding the development of the pancreas.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

膵島移植は一型糖尿病の根本的な治療法になりうる可能性があるが、絶対的なドナー不足がこの普及を妨げている。ドナーに依存しない膵島の供給源として、多能性幹細胞からの膵β細胞の分化誘導方法が研究されている。しかし、現状では分化誘導効率が低く、未分化細胞の混入などの安全性の問題、およびコストの問題などを抱える。本成果を応用することで、分化誘導効率を向上させ、細胞の安全性を高めることが期待できる。