2023 Fiscal Year Final Research Report

The optimization of physiological stimulation for ex vivo lung bioengineering and the establishment of an international foundational study network

Research Project

PDF

Project/Area Number	20KK0255
Research Category	Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 90:Biomedical engineering and related fields
Research Institution	Nagasaki University
Principal Investigator	TSUCHIYA TOMOSHI 長崎大学, 医歯薬学総合研究科(医学系), 客員教授 (30437884)
Co-Investigator(Kenkyū-buntansha)	土肥良一郎長崎大学, 病院(医学系), 助教 (00817786) 溝口聡長崎大学, 病院(医学系), 医員 (20816706) 渡邉洋之助長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (30457551)
Project Period (FY)	2020-10-27 – 2024-03-31
Keywords	肺再生 / 医工学 / 脱細胞化 / 再細胞化 / 再生医学 / バイオリアクター / バリア機能 / 接着因子
Outline of Final Research Achievements	In the field of organ regeneration/transplantation medicine, organ regeneration is performed by "decellularization" of organs and "recellularization" to reconstitute tissues using the remaining tissue scaffolds as a template. In this study, we focused on a new factor, "moderate physiological stimulation. We monitored pulmonary blood flow in the regenerated lungs and found that increasing perfusion stimulated capillary cell bioproduction. The appropriate combination of cell types increases the barrier function of the regenerated lung epithelium and that the morphology of the alveoli in the regenerated lungs approaches normal. In a rat single lung resection model, the results suggest that mechanical stimulation induces the expression of methanotrophic genes in mesothelial cells, which act from pleural mesothelial cells to alveolar stem cell-like Alveolar Tuft Cells, resulting in lung regeneration.
Free Research Field	呼吸器外科学
Academic Significance and Societal Importance of the Research Achievements	本研究目標の達成は、臓器不足に悩まされる世界の再生医療への大きな貢献となる。しかし、臓器再生研究は多くの技術や知識を必要とし、国際的に取り組む重要かつ緊急な課題である。本構想では、移植時に破綻しないバリア機能を持つ肺胞を作り出す、灌流を維持できる毛細血管を再構築する、という関連する２つの課題を克服するために、臓器への機械的刺激(メカニカルストレス)の付加を手掛かりに、長崎大学チームとYale大学チームそれぞれの強みを生かした共同研究を行う。