Development of primitive-gut-derived organ bioengineering methods based on spheroid designing.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21597
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Okamoto Ryuichi 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (50451935)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: iPS細胞 / 原腸由来臓器 / スフェロイド

Outline of Final Research Achievements

Through our development of a highly efficient iPS cell-derived primitive-gut spheroid production and the analysis of their fusion/differentiation potential, we have optimized the spheroid-forming method. Also, we have succeeded in developing a method to produce a highly uniform and abundant number of primitive-gut spheroids under the control of their final size and regulate the differentiation of those spheroids. In addition, we have confirmed that those or spheroids can engraft within a certain period after transplantation to severely immunodeficient mice, and also acquire tissue-specific functions and increase their tissue size in vivo. From these results, we have succeeded in developing methods and essential knowledge to induce differentiation from human iPS cells to primitive-gut-derived tissue via the definitive endoderm with the help of both in vitro and in vivo experimental environments.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

高い効率で任意のサイズを有する原腸スフェロイドを作成可能であるばかりでなく、同法で作成したスフェロイドが極めて高い融合指向性と体外環境における原腸由来臓器への分化能を兼ね備えていることを利用し、任意の形状・サイズを有する原腸由来前駆体から原腸由来組織を分化誘導する「スフェロイド・デザイニング」を可能とするための基盤となる知見が確立された。