2022 Fiscal Year Final Research Report

Development of a novel method of regenerative medicine using cardiac anlage differentiated from human oral mesenchymal muse cells

Research Project

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Project/Area Number	20H03761
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 55030:Cardiovascular surgery-related
Research Institution	University of Tsukuba
Principal Investigator	Suzuki Yasuyuki 筑波大学, 医学医療系, 教授 (60344595)
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) 松丸祐司筑波大学, 医学医療系, 教授 (70323300) 松村明筑波大学, 医学医療系, 客員教授 (90241819) 渡邊美穂大阪公立大学, 大学院医学研究科, 特任助教 (20845317) 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)	2020-04-01 – 2023-03-31
Keywords	歯髄幹細胞 / 胚様体 / 胚子様構造体 / 心原基
Outline of Final Research Achievements	There are no reports of transplanted differentiated induced cardiomyocytes maintaining their function for a long period of time. The applicants considered that this was due to the lack of a method to obtain the many types of cells that make up the heart by differentiation induction, and considered it essential to obtain cardiomyoblasts from human dental pulp stem cells, which are rich in pluripotent stem cells. First, embryonic growth factor (EmbGF) was prepared, which was used to produce embryoid bodies resembling blastocysts by canopy culture of dental pulp stem cells. These embryoid bodies were reflux-cultured with EmbGF to produce embryoid-like structures with beating hearts. The beating cardiac primordium was harvested to obtain cardiomyocytes, cardiac valve leaflets and stimulatory conduction system. The stimulo-conducting system cells readily formed nerve bundle-like structures in culture. Cardiomyocytes proliferated in culture and formed a myocardial network.
Free Research Field	心原基を分化誘導する医学再生医療
Academic Significance and Societal Importance of the Research Achievements	あらゆる種類の心機能不全に陥った患者を再生医療で救済するための全く新しい移植細胞採取法を開発した。すなわち万能細胞が多い歯髄幹細胞を天蓋培養して胚様体を作製し、これを成育させて胚子様構造体を作製して、そこから心臓を構成する細胞をone set有する心原基を採取して再生医療に供するものである。心原基を再生医療の細胞源にすればあらゆる心疾患に対処できる新規心臓再生医療の創成となり、その社会的貢献は計り知れない。またHLAホモドナーの歯髄あるいはUDC化したiPS細胞から胚子様構造体を分化生育すれば、他家移植の再生医療が可能になりその社会的意義は大きい。