Lung Organoid culture method concerning meso-endodermal interaction

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09299
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Tohoku University
• Principal Investigator: Jun-ichi FUNAHASHI 東北大学, 加齢医学研究所, 准教授 (00270827)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: オルガノイド / 肺の再生 / 間葉系前駆細胞 / 共培養

Outline of Final Research Achievements

Making organs from human pluripotent stem cells (iPSC) is a challenging approach for developmental biology, cell biology and regenerative medicine.
There are several reports that describe induction of organoid such as gastric, intestinal, pancreatic, liver bud and recently lung. In most of the cases, they first tried to induce endoderm, then further differentiation of endoderm and mesenchyme which supports endoderm. However, in normal development, most of the mesenchyme which works for maintenance of differentiated endoderm is derived from mesoderm. We thought that this discrepancy introduces limitation for further differentiation. Based on this idea, we developed step-wise protocol to make highly organized lung form iPSC. As a first step, we attempted to re-produce the lung organoid that was reported before. In the second step, we induced lung mesenchyme from mesoderm which is derived from iPSC. In the last step, these tissues were combined to produce mature lung.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

これまで多能性幹細胞を二つの異なる胚葉に分化させ、それらを組み合わせて培養する研究はほとんど行われておらず、この手法の有用性が明らかとなったことには学術的意義がある。また、自己あるいは組織抗原の一致するiPS細胞から人工的に臓器を作成することが可能になれば、臓器移植の代替手段の開発につながることが期待できる。