Analysis of homeostasis mechanisms using a human in vitro multi organ model

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H01050
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Watanabe Mamoru 東京医科歯科大学, 高等研究院, 特別栄誉教授 (10175127)
• Co-Investigator(Kenkyū-buntansha): 油井 史郎 東京医科歯科大学, 統合研究機構, 准教授 (00383886) ; 柿沼 晴 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30372444) ; 鬼澤 道夫 福島県立医科大学, 医学部, 助教 (30783352) ; 土屋 輝一郎 筑波大学, 医学医療系, 教授 (40376786)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ヒトオルガノイド / 臓器間制御機構 / 臓器共培養

Outline of Final Research Achievements

Culture system of human colon cells and human iPS-derived liver cells was established respectively. We are examining whether colon cells and liver cells can be cultured in the same culture medium. After examining various culture conditions, we confirmed that colon cells and liver cells can be co-cultured, and constructed a system in which the interaction can be analyzed. We have also constructed disease models for both liver and colon cells, and have established a system that can analyze the effects between organs in disease by co-culturing normal colon and diseased liver, or diseased colon and normal liver. Furthermore, by transplanting human cells into mice, we have constructed chimeric mice with diseased human cell organs. These results are expected to advance our understanding of the pathophysiology of inter-organ regulatory mechanisms in human diseases.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

ヒト疾患において臓器間制御機構の関与が注目されているが、多くの研究は実験動物を用いたin vivoモデルにより得られた結果である。ヒト細胞を用いた臓器間制御機構の解析は困難であるが、我々はその擬似モデルとして多臓器共培養システムやヒト多臓器保持マウスを構築し、臓器間制御機構を明らかにすることは学術的に意義が高いと考える。より、ヒトに近い実験系を作成することがヒト疾患の病態解明に有用な手法であり、疾患の全身的な理解が進むことは社会的にも意義が高い。