Mechanisms of proliferation and differentiation of spiral ganglion neural stem cells and their application to hearing regeneration.

Research Project

Project/Area Number	18K16845
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 56050:Otorhinolaryngology-related
Research Institution	Kyushu University
Principal Investigator	Tetsuro Yasui 九州大学, 医学研究院, 共同研究員 (60803468)
Project Period (FY)	2018-04-01 – 2022-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	再生医療 / 聴覚再生 / 幹細胞 / 再生・修復 / 耳科学 / 聴覚医学 / ラセン神経節ニューロン / 聴力再生 / ラセン神経節 / 聴神経 / 神経幹細胞 / エピジェネティクス / 内耳再生 / 聴覚神経 / 螺旋神経節細胞
Outline of Final Research Achievements	It has been believed that adult mammalian spiral ganglion (SG) do not regenerate spiral ganglion nueron(SGN) (Lang et al. Sci Rep 2015). However, the applicants have overturned this prevailing theory and demonstrated the existence of neural stem/progenitor cells (NS/PCs) in adult mice that can initiate proliferation and produce SGNs in response to SGN injury induced by a drug (ouabain). Furthermore, by controlling their proliferation, differentiation, and survival, they succeeded in efficient SGN regeneration and hearing improvement (JCI Insight 2021). Since cochlear hearing loss, which accounts for the majority of sensorineural hearing loss, also causes secondary degeneration and loss of SGNs, we believe that hearing regeneration by highly efficient SGN replacement is comparable to hair cell regeneration.
Academic Significance and Societal Importance of the Research Achievements	全世界に難聴者は4億7000万人と言われ、全人口の6％に相当する。世界で最も高齢化が進んでいる日本では、2018年に65歳人口が総人口の28.1%を占め、この割合は2065年には約40%に達すると予想される。また難聴は必然的にコミュニケーション障害を引き起こし、社会的孤立、うつ病、身体的・認知的機能の低下と関連し、その社会的損失も極めて大きい。特に後迷路性難聴は言語聴取に劣り、代償が困難であるため、QOLの著しい低下を招くが、根本的な治療法は現在存在していない。申請者らの報告は、変性・死滅する自己SGNを保護・再生させるものであり、今後の後迷路性難聴に対する根本的かつ嚆矢的再生治療となりうる。