Inner ear cell therapy by activated stem cell homing

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K21662
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Juntendo University
• Principal Investigator: Kamiya Kazusaku 順天堂大学, 医学部, 准教授 (10374159)
• Project Period (FY): 2020-07-30 – 2024-03-31
• Keywords: 遺伝性難聴 / 人工多能性幹細胞 / 内耳 / ギャップジャンクション / 分化誘導 / 遺伝子難聴

Outline of Final Research Achievements

In the previous study, we have developed a mouse model with a CX26 defect especially in inner ear, which forms inner ear gap junctions, considered the onset mechanism due to gap junction disruption, and developed an inner ear gene therapy method that restores hearing by restoring this abnormal gap junction through gene transfer. In order to introduce inner ear progenitor cells made from stem cells into the cochlear tissue, it is important to widely apply the cell guidance molecular mechanism called stem cell homing that is correct for the cochlear tissue. We developed a technology that efficiently restores the correct cells to the inner ear tissue associated with hereditary hearing loss by increasing the amount of hearing loss, thereby restoring hearing.

Free Research Field

難聴

Academic Significance and Societal Importance of the Research Achievements

本研究では世界で最も高頻度に発生する難聴原因遺伝子GJB2の遺伝子改変難聴モデルに対し、研究代表者が開発した幹細胞移植法に更に内耳ホーミング機構を応用して内耳への細胞導入効率を飛躍的に高めることにより、これまで成功例のない遺伝性難聴に対する聴力回復法の開発を試みる挑戦的な研究である。iPS細胞は成体細胞の初期化により作成でき、難聴患者の血液や皮膚組織からの樹立が可能なため既に多くの疾患において実用化研究が進められており、骨髄間葉系幹細胞も安全で移植効率を高めることが知られているためどちらも有用な移植細胞として活用できる。