Generation of the methods of safety evaluation for alveolar organoid transplantation

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H05084
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Kyoto University
• Principal Investigator: Gotoh Shimpei 京都大学, 医学研究科, 特定准教授 (50747219)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 肺 / ヒトiPS細胞 / 移植 / オルガノイド / 肺胞

Outline of Final Research Achievements

Through this project, the methods of generating human induced pluripotent stem (iPS) cell-derived alveolar epithelial cells and their long-term culture have been established. The differentiation process from the lung progenitor cells to alveolar epithelial cells was delineated at the single-cell level. Not only human iPS cell-derived alveolar type II (iAT2) cells but also alveolar type I (iAT1) cells were identified. Each transcriptome was compared and thereby the method of directing differentiation from iAT2 to iAT1 cells was established. On the other hand, iAT2 cells can possess and secrete lamellar bodies, organelles to restore pulmonary surfactant. Gene editing technology has made it possible to establish disease modeling of rare hereditary diseases in a dish. And a method of safe transfer of alveolar organoids intratracheally to mouse was developed and the iPSC-derived cells were successfully engrafted on the living mouse lung without generating tumor-like lesion.

Free Research Field

幹細胞生物学、呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

ヒト由来肺胞上皮細胞は長年、研究利用の難しい細胞だったが、多能性幹細胞を用いることで、必要時に必要な数のヒト肺胞上皮細胞を分化誘導して研究利用が可能になった。さらに遺伝子改変も行えるようになったことで、疾患研究への波及効果も見出せるようになった。さらにヒトiPS細胞由来の肺胞上皮細胞をマウスに定着させることもでき、特に腫瘍性変化を伴うことはなかった。これらの成果により呼吸器における再生医療や創薬に向けてさらなる研究の発展を期待できるようになった。