2021 Fiscal Year Final Research Report
Development of intestinal graft production and transplantation method using human iPS cell-derived self-organization intestinal organoids.
Project/Area Number |
20K22920
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0903:Organ-based internal medicine and related fields
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
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Project Period (FY) |
2020-09-11 – 2022-03-31
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Keywords | 腸管スフェロイド / iPS細胞 / 腸管グラフト / 自己組織化 |
Outline of Final Research Achievements |
Self-organization intestinal spheroids derived from human iPS cells were successfully auto-fused into intestine-like tubular spheroids on a special low-attachment micro groove plate. Efficient culture conditions to maintain a large structure of tubular intestinal spheroids were also found by introducing rotational suspension culture using a bioreactor. The established intestinal spheroids were transplanted into immunodeficient mice for further tissue maturation in vivo. We were able to establish a stable transplantation method of intestinal tubular spheroids to the mesenteric region. The intestinal spheroids grew and matured into intestinal graft tissue after transplantation.
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Free Research Field |
消化器内科学
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Academic Significance and Societal Importance of the Research Achievements |
iPS 細胞由来の「自己組織化腸管スフェロイド」を用い、実際の移植治療に応用可能な腸管グラフトへと成熟させる技術の開発を目指す本研究は、世界で初めての管腔構造を有する腸管グラフトを作出し、免疫不全マウス実験系を用いたグラフト成熟技術の確立により、体外で作出した腸管グラフトを移植することで腸機能を回復させるという新規治療のPOC (Proof Of Concept) 取得を目指したものである。本研究の成果を発展させることで、広範な腸機能の消失を伴う短腸症候群に対する根本的治療の基盤技術開発のみならず、腸上皮幹細胞による体外での自律的な3次元臓器形成、機能獲得に関する重要な知見の創出が期待される。
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