Generation of inner ear hair cells toward cell transplantation using pluripotent stem cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H05482
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Nara Medical University
• Principal Investigator: Yoshikawa Masahide 奈良県立医科大学, 医学部, 教授 (50230701)
• Co-Investigator(Kenkyū-buntansha): 北原 糺 奈良県立医科大学, 医学部, 教授 (30343255) ; 王寺 幸輝 奈良県立医科大学, 医学部, 准教授 (50343421) ; 和中 明生 奈良県立医科大学, 医学部, 教授 (90210989)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 内耳 / 再生医学 / 有毛細胞 / 幹細胞 / 耳科学 / 分化誘導 / 細胞培養 / 聴覚再生

Outline of Final Research Achievements

The self-renewal capability of inner ear hair cells in mammals is extremely poor, thus stem cells harboring an ability to generate inner ear hair cells is a promising treatment option for damaged inner ear hair cells. We have successfully developed a new method for in vitro production of inner hair cells from pluripotent stem cells. In the present study, the mechanism of differentiation and possibility of cell transplantation using isolated cochlea tissue samples were investigated. The results showed that secretory factors related to resident cells in the inner ear facilitated differentiation of stem cells into inner ear hair cells, with several candidates determined based on RNA-sequence analysis. In addition, analysis of the co-culture with embryonic stem cell-derived inner ear hair cells and isolated cochlea tissues revealed cell settlement in the cochlea, suggesting the applicability of this in vivo method for cell transplantation therapy.

Free Research Field

再生医学

Academic Significance and Societal Importance of the Research Achievements

難聴治療の鍵となる内耳有毛細胞に着目し、様々な細胞に分化可能な多能性幹細胞から効率良く誘導する方法を開発した。本法は、これまでの方法に比べ簡便かつ高効率である。内耳細胞の再生研究および細胞移植治療に用いる細胞源確保に十分貢献できる成果である。本研究で開発した手法を、臨床応用が開始されたヒトiPS細胞へ適応することで、今後の耳科領域における研究を更に発展させる可能性がある。