Application of transplantation of hiPSC-derived airway epithelial sheets to nasal sinuses

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18279
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Kyoto University
• Principal Investigator: Kitada Yuji 京都大学, 医学研究科, 医員 (50869584)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 鼻・副鼻腔 / 移植治療 / ヒトiPS細胞 / 線毛上皮細胞 / コラーゲンビトリゲル / ヌードラット

Outline of Final Research Achievements

The purpose of this study is to create a nasal mucosal humanized rat model, which was necessary for the establishment of basic technology of treatment for nasal mucosal dysfunction and the analyses of pathological mechanisms by the transplantation of human iPS cell-derived airway epithelia into the nasal mucosal defect of the immunodeficient rat. For this purpose, we optimized the conditions for nasal respiratory epithelial exfoliation such as depth and area of the scraping area, and the conditions for transplantation such as cell lines, scaffolds, and recipient rats. After transplantation into six immunodeficient rats, four rats showed human iPS cell-derived engrafted cells, and it was confirmed that these human iPS cell-derived engrafted cells contained the cells that constitute the airway epithelia. In conclusion, we succeeded in engraftment of human iPS cell-derived airway epithelia in the nasal cavity of immunodeficient rats.

Free Research Field

鼻科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は遺伝性疾患や外傷などによる粘膜機能不全に対する移植治療のための基盤技術の確立として有用であり、移植細胞を嗅上皮に変えることで嗅覚異常への応用も可能であり、波及効果が期待できる。また鼻腔は管腔面が気層で呼吸の刺激にさらされる特殊な環境であるため、鼻腔ヒト化ラットは培養細胞を用いた培養液中での治療薬の検証よりもより生体に近い効果を検証可能であり、創薬研究にも有用である。COVID-19における嗅覚障害の発症メカニズムの解析や治療薬の検証にも応用可能であり、社会的意義は大きいと考えられる。