Generation of pancreatic exocrine cells from iPS cells and delivery of pancreatic digestive enzymes into the gastrointestinal tract by pancreatic exocrine tissue transplant

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10688
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyorin University (2018-2019); The University of Tokyo (2017)
• Principal Investigator: Yoshihiro Sakamoto 杏林大学, 医学部, 教授 (70343746)
• Co-Investigator(Kenkyū-buntansha): 松浦 勝久 東京女子医科大学, 医学部, 准教授 (70433993)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: iPS細胞 / 膵外分泌機能不全 / 再生医療

Outline of Final Research Achievements

Exocrine pancreatic insufficiency, caused by disease-induced loss of pancreatic exocrine cells, may be treated through regenerative stem cell technologies that facilitate the production of pancreatic exocrine cells from induced pluripotent stem cells (iPSCs). However, delivering the digestive enzymes produced in the transplanted cells to the gastrointestinal tract remains a challenge. Human iPSCs were differentiated into pancreatic exocrine cells by stage-specific treatment with growth factors and chemical compounds, and the differentiated pancreatic cells were implanted into the gastric submucosal space of nude rats with ablation of muscularis mucosa. The transplanted cells were engrafted, and amylase was detected in the gastric juice in some cases.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

本研究では、1）iPS細胞から膵外分泌細胞を分化誘導することが可能であった、2）膵外分泌細胞の機能的に胃粘膜下層へ同型移植することが可能であった、3）同手法を用いてiPS細胞由来膵外分泌細胞をNudeラットの胃粘膜下層へ移植し、機能的な移植が可能であることが示唆された。近年の幹細胞技術の発展により、様々な疾患に対する再生医療学的アプローチが期待されている。本研究の結果は、膵外分泌機能不全に対する再生医療学的なアプローチの臨床応用につながることが期待できると考えている。