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

• 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
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: iPS / 膵島 / iPS細胞 / 分化誘導

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.

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。

Research Products

• [Presentation] ヒトiPS細胞由来膵内分泌前駆細胞に発現する細胞膜タンパクの機能解析 (2019)
  • Author(s): 渡邊亜美, 田中杏奈, 山下-菅原泉, 宮島篤
  • Organizer: 第18回日本再生医療学会総会
• [Presentation] Differentiation of functional islets from human iPS derived endocrine progenitor cells. (2018)
  • Author(s): Ami Watanabe, Anna Tanaka, Atsushi Miyajima
  • Organizer: ISSCR Annual Meeting 2018
  • Int'l Joint Research
• [Presentation] ヒトiPS細胞由来膵内分泌前駆細胞の純化と機能解析 (2018)
  • Author(s): 渡邊亜美, 田中杏奈, 宮島篤
  • Organizer: 第17回日本再生医療学会
• [Presentation] ヒトiPS細胞由来の膵内分泌前駆細胞を用いた機能的膵島分化誘導系の開発 (2017)
  • Author(s): 渡邊亜美, 田中杏奈,大坪寛之, 太田正広, 山下-菅原泉, 三谷幸之介, 中西真人, 岡崎 康司, 宮島篤
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 仙台国際センター（宮城県仙台市)
  • Year and Date: 2017-03-07
• [Presentation] Differentiation of functional islets from human iPS cells and hiPS-endocrine progenitor cells in vitro. (2016)
  • Author(s): Ami Watanabe, Anna Tanaka, Hiroyuki Otsubo, Masahiro Ohta, Yzumi Yamashita-Sugahara, Kohnosuke Mitani, Mahito Nakanishi, Yasushi Okazaki, Atsushi Miyajima
  • Organizer: ISSCR 2016
  • Place of Presentation: san francisco, california, USA
  • Year and Date: 2016-06-22
  • Int'l Joint Research