Mechanism of action and effects of induced pluripotent stem cell-derived neural crest cells on axonal regeneration

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11703
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Aichi Gakuin University (2017-2018); Nihon University (2016)
• Principal Investigator: TORIUMI Taku 愛知学院大学, 歯学部, 講師 (40610308)
• Co-Investigator(Kenkyū-buntansha): 本田 雅規 愛知学院大学, 歯学部, 教授 (70361623) ; 磯川 桂太郎 日本大学, 歯学部, 教授 (50168283)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ヒトiPS細胞 / 神経堤細胞 / 末梢神経損傷 / 下歯槽神経

Outline of Final Research Achievements

This study aimed to clarify the effectiveness of human induced pluripotent stem cell-derived neural crest cells (NCC) transplantation in the recovery of sensory function and regeneration after peripheral nerve injury. Inferior alveolar nerve transection was performed in rats, and the gap was bridged using NCC or rat Schwann cell-seeded collagen tube. In the NCC group, the threshold of head-withdrawal reflex to mechanical stimulation of the lower lip began decreasing on day 3 post-transplantation. Immunofluorescence analysis revealed human mitochondria and S-100β double-positive cells in regenerating axons in the middle of the NCC-seeded tubes on day 14 post-transplantation. In addition, the number of neurofilament 200-positive fibers was not significantly different between the NCC and rat Schwann cell transplantation group. These findings suggest that human iPS cell-derived NCC might contribute to guiding axonal regeneration and sensory function recovery.

Free Research Field

再生歯学，幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

神経欠損部位ではその軸索断端から神経誘導因子が放出されると考えられており、移植したiPS細胞由来神経堤細胞は生体内の場の環境に適応し、シュワン細胞へ分化する可能性が本研究成果により示唆された。現在、京都大学iPS研究所では『再生医療用iPS細胞ストックプロジェクト』を進めており、臨床応用を踏まえ、高頻度のHLA型を持つ個人からiPS細胞を作製・保存している。iPS細胞を利用した再生医療は今後さらなる進展が期待されており、利用が困難なヒトシュワン細胞に代わり、ヒトiPS細胞由来神経堤細胞は末梢神経損傷のための細胞治療ソースとなり得る可能性が考えられる。