2023 Fiscal Year Final Research Report

A mini-organ culture system with cancer immune microenvironment recapitulating in vivo

Research Project

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Project/Area Number	22K19564
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research Institution	Yamaguchi University
Principal Investigator	Seiki Makoto 山口大学, 大学院医学系研究科, 教授 (50226619)
Co-Investigator(Kenkyū-buntansha)	永野浩昭山口大学, 大学院医学系研究科, 教授 (10294050) 浅岡洋一山口大学, 大学院医学系研究科, 講師 (10436644) 宮本達雄山口大学, 大学院医学系研究科, 教授 (40452627) 硲彰一山口大学, 医学部, 特別医学研究員 (50253159) 柴田健輔山口大学, 大学院医学系研究科, 講師 (50529972)
Project Period (FY)	2022-06-30 – 2024-03-31
Keywords	YAP / メカノホメオスターシス / 力学恒常性 / がん免疫
Outline of Final Research Achievements	Current cancer treatment often proceeds by trial and error, testing standard therapies and confirming their efficacy as treatment progresses. If effective drugs could be identified in advance, it would be possible to initiate treatment with improved prognosis and reduced suffering. Therefore, utilizing the mechanism of YAP-mechanohomeostasis, which we discovered as an organ-level mechanical control mechanism, we aim to establish a culture system for the cancer immune microenvironment, which is the source of resistance to anticancer drugs. To achieve this, we (1) created simplified mini-intestines, (2) developed a human mini-liver platform with artificial capillaries, and (3) introduced a novel method for spatiotemporal mechanical measurements that are non-contact and label-free to evaluate its self-organizing mechanical control. This method enables the creation of mini-organs containing immune cells.
Free Research Field	がん生物学
Academic Significance and Societal Importance of the Research Achievements	(1)患者ごとの生体を反映したがん免疫微小環境培養系を創出する:本研究で創出するがん免疫微小環境培養系を用いて、治療前に有効な薬剤を予測できれば、患者の予後を改善し、身体的負担、医療費削減につながることから、挑戦的研究として大きな意義がある。(2) 臓器の力学制御による新しい視点からの治療開発: 慢性炎症などによる線維化は組織を硬くしてYAPを活性化する。YAPは、細胞の増殖・分化だけでなく代謝にも変化を与え、免疫抑制、がん進展を起こす。そこで、本がん免疫微小環境培養系は、”がん免疫組織の力学制御”という新しいコンセプトの治療創出へも役立つと考えられる。