2023 Fiscal Year Final Research Report

Muscle regeneration therapy using dedifferentiated fat cells-derived exosome for anal sphincter disorders

Research Project

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Project/Area Number	21K08606
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55010:General surgery and pediatric surgery-related
Research Institution	Nihon University
Principal Investigator	HOSOKAWA Takashi 日本大学, 医学部, 助教 (50870094)
Co-Investigator(Kenkyū-buntansha)	松本太郎日本大学, 医学部, 教授 (50366580) 金田英秀日本大学, 医学部, 助教 (30598967) 上原秀一郎日本大学, 医学部, 教授 (00448060)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	肛門括約筋 / 脱分化脂肪細胞 / exosome / 筋再生治療
Outline of Final Research Achievements	In vitro, C2C12 cells, which are myoblasts derived from mice, were divided into control group, DFAT condition medium group, medium group with DFAT-derived exosome, and DFAT condition medium group without exosome. The expression of MyoD and Myogenin were compared by RT-PCR. In the DFAT exosome group, both MioD and Myogenin were up-regulated, although not significantly. In vivo, the effects of DFAT and DFAT-derived exosomes were examined in a rat model of anal sphincter dysfunction in which cardiotoxin was administered topically around the anus. The anal pressure of rats with anal sphincter dysfunction was evaluated using manometry after topical administration of DFAT or DFAT-derived exosome, and it was confirmed that the anal pressure of rats treated with topical DFAT increased earlier than that of the control group. However, the anal pressure in the exosome group did not show a constant tendency to increase.
Free Research Field	再生医療
Academic Significance and Societal Importance of the Research Achievements	肛門括約筋障害は、便秘や便失禁などの排便機能障害をきたすが、現行の治療法では治療に難渋する例が多い。特に小児外科領域における直腸肛門奇形は、先天的な肛門括約筋低形成による機能障害も認める事から、肛門括約筋の再生医療が新規治療法として期待される。近年、再生医療の中でも、そのシグナル伝達の1つとしてexosomeが注目されている。本研究ではDFATから放出されるexosomeが筋分化誘導に与える影響を解明し、より効果的に肛門括約筋機能を改善する方法を検討する。DFAT由来のexosomeによる肛門括約筋の機能改善効果を示す事で、直腸肛門奇形患者の排便機能の改善に繋がることが期待される。