Lung regeneration by airway transplantation of organoids made from rat fetal lung cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18219
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: The University of Tokushima
• Principal Investigator: MATSUMOTO Daisuke 徳島大学, 大学院医歯薬学研究部(医学域), 特任助教 (10761893)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 再生 / 幹細胞 / 肺 / オルガノイド / 気道投与

Outline of Final Research Achievements

17-day-old GFP fetal rat lung tissues were harvested to generate lung organoids. The organoids were used as donors after 6 days culture, and female LEW rats were used as recipients. A tube was inserted into the trachea, and 0.4ml DMEM including fetal rat lung organoids was administered intratracheally. We harvested the both lungs on 3 days, 1, 2, 4, and 8 weeks, and histologically evaluated. The GFP (+) areas were observed, and the expressions of Podoplanin, Surfactant protein C, Foxj1 and club cell secretory protein were confirmed by immunostaining, indicating that the grafts could survive and differentiate in recipients’ lung. The fetal lung organoids were administrated into bleomycin-induced pulmonary fibrosis model as well. At 4 weeks after administration, the GFP (+) alveolar-like structure were confirmed in the fibrotic lungs such as shown in the normal lungs.

Free Research Field

医歯薬学　呼吸器外科学

Academic Significance and Societal Importance of the Research Achievements

胎仔肺組織によりオルガノイドが形成でき、肺に生着することが確認できたため、今後の再生医療において重要な細胞ソースの一つとなる可能性が示された。また、気管内投与による移植にも成功し、ラット以外に対しても低侵襲で効率の良い移植方法として実現性が高いものと考えられ、将来的に選択肢の一つになりうると思われる。新たな肺再生医療の基礎的知見が得られ、今後の研究につながる成果であったと考える。