Development of cell transplantation therapy using pluripotent stem cells for severe vestibular disorders

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16903
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Nara Medical University
• Principal Investigator: Sakagami Masaharu 奈良県立医科大学, 医学部附属病院, 研究員 (50745437)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 内耳有毛細胞 / ES細胞 / 内耳再生 / 分化誘導 / 前庭

Outline of Final Research Achievements

Vestibular hair cells (V-HCs) in the inner ear have important roles and various functions. When V-HCs are damaged, crippling symptoms, such as vertigo, visual field oscillation, and imbalance, are often seen. Recently, several studies have reported differentiation of embryonic stem (ES) cells, as pluripotent stem cells, to HCs, though a method for producing V-HCs has yet to be established. In the present study, we used vestibular cell conditioned medium (V-CM) and effectively induced ES cells to differentiate into V-HCs. Expressions of V-HCrelated markers (Math1, Myosin6, Brn3c, Dnah5) were significantly increased in ES cells cultured in V-CM for 2weeks, while those were not observed in ES cells cultured without V-CM. On the other hand, the cochlear HCrelated marker Lmod3 was either not detected or detected only faintly in those cells when cultured in V-CM. This results demonstrate that V-CM has an ability to specifically induce differentiation of ES cells into V-HCs.

Free Research Field

内耳

Academic Significance and Societal Importance of the Research Achievements

本研究により、前庭細胞由来液性因子を用いることで、前庭有毛細胞への特異的分化誘導制御が実現可能となった。この新しい知見は、内耳再生医学の基礎的視点から前庭有毛細胞の分化・再生メカニズムを解明する上で重要と考えられる。