Development of treatment in acute stroke with neuronal cells derived from primary cell culture of human dental pulp and gingiva

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09450
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: University of Tsukuba
• Principal Investigator: Matsumaru Yuji 筑波大学, 医学医療系, 教授 (70323300)
• Co-Investigator(Kenkyū-buntansha): 石川 博 筑波大学, 医学医療系, 研究員 (30089784) ; 丸島 愛樹 筑波大学, 医学医療系, 講師 (40722525) ; 武川 寛樹 筑波大学, 医学医療系, 教授 (80173558) ; 豊村 順子 筑波大学, 医学医療系, 研究員 (80645630) ; 大山 晃弘 筑波大学, 医学医療系, 研究員 (90538232)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 脳卒中 / 再生医療 / 歯髄 / 間葉系幹細胞 / 神経系細胞

Outline of Final Research Achievements

Dental pulp stem cells were generated from human dental pulp and induced to differentiate into nervous system cells. The nervous system cells were positive for neural stem cells, astrocytes, immature and mature neuronal cells and oligodendrocytes markers of the central nervous system. The cells were electrically active, had high VEGF expression and were hypoxia tolerant. In an experimental system of direct transplantation of cells by an immunocompetent mouse model of cerebral infarction, transplanted nervous system cells were viable in the cerebral infarct lesion at 28 days after transplantation, confirming differentiation of the transplanted cells into astrocytes and immature and mature neuronal cells. We found the possibility of axonal elongation from transplanted neurons in the subcortex into the host brain and the establishment of a neuronal network.

Free Research Field

脳神経外科

Academic Significance and Societal Importance of the Research Achievements

智歯等で抜歯を受けたヒト歯髄を用いることで、細胞源の倫理的問題を解決できる。ヒト歯髄から神経幹細胞、神経系細胞を分化誘導する新技術を特許出願（神経系細胞含有製剤の製造方法：特願2019-91625）、PCT出願（神経系細胞集団、神経系細胞含有製剤およりそれらの製造方法：PCT/JP2020/019290)を行い、指定国移行、権利化を行ったことで、今後、新たな歯髄由来の神経幹細胞や神経系細胞を用いた神経系の再生医療が可能になった。これらの研究成果は、学術論文として受理、掲載された。