2021 Fiscal Year Final Research Report

Development of treatment for fecal incontinence using non-cultured human adipose derived mesenchymal stem cells.

Research Project

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Project/Area Number	19K09155
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Dokkyo Medical University
Principal Investigator	Ishizuka Mitsuru 獨協医科大学, 医学部, 准教授 (20382963)
Co-Investigator(Kenkyū-buntansha)	清水崇行獨協医科大学, 医学部, 助教 (50622198) 窪田敬一獨協医科大学, 医学部, 教授 (70260388) 山西友典獨協医科大学, 医学部, 教授 (90220425) 井上健一獨協医科大学, 医学部, 准教授 (90587974) 岸本聡子獨協医科大学, 医学部, 講師 (10511488)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	再生医療 / 便失禁 / 脂肪組織由来再生幹細胞 / 間質血管細胞群 / 内肛門括約筋 / 肛門括約筋障害モデル動物
Outline of Final Research Achievements	Vaginal distension (VD) rat was used as a model of damaged anal sphincter function (ASF). The adipose SVF was separated from the inguinal fat of syngeneic green fluorescent protein (GFP) transgenic rats and delivered into the internal anal sphincter (IAS) of VD rats. The maximum resting pressure (MRP) was　evaluated after VD treatment. GFP-transfected human-adipose derived mesenchymal stem cells (ADSC) were transplanted into the IAS of nude rats. The mean MRP (during catheter withdrawal) of VD rats was significantly lower than that of control rats, and SVF injection normalized it 4 days after treatment: Control: 5.66±0.98, VD: 4.04±1.28, VD+SVF: 5.92±1.28 (mmHg, control vs. VD: P = 0.039; VD vs. VD+SVF: P = 0.007). The transplanted syngeneic SVF survived for 10 days. Transplanted xenogeneic human-ADSCs survived in the IAS of nude rats for 4 and 10 days. Syngeneic and heterotopic transplanted ADSCs engrafted in the IAS and ameliorated damaged ASF in a rat model of VD.
Free Research Field	下部消化管治療
Academic Significance and Societal Importance of the Research Achievements	本研究の成果から下部尿路障害の治療モデル動物で行われた結果と同様の結果を得ることができた。腹圧性尿失禁の治療に実際に患者さんの脂肪組織由来間葉系幹細胞が治験として用いられており、近い将来保険収載される可能性も予想されることから脂肪組織由来間葉系幹細胞を用いた肛門括約筋障害に基づく便失禁の新たな治療方法として今回の研究の成果は今後発展していくと考えられ、再生医療に基づく新たな便失禁の治療方法の誕生を予見できたことについては国内外に与えるインパクトは極めて大きいと考えられる。