| Project/Area Number |
21K08596
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ISHIBASHI Hiroki 徳島大学, 大学院医歯薬学研究部(医学域), 講師 (20314867)
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| Co-Investigator(Kenkyū-buntansha) |
池本 哲也 徳島大学, 病院, 教授 (20398019)
齋藤 裕 徳島大学, 病院, 講師 (50548675)
森 大樹 徳島大学, 病院, 特任助教 (70448330)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 鎖肛 / 直腸肛門奇形 / 排便機能障害 / 脂肪由来Schwann様細胞 / ADSC / 排便障害 / Schwann細胞 / 脂肪由来幹細胞 / mTORC1 / HMGB1 / シュワン様神経細胞 |
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| Outline of Research at the Start |
転写因子を調節するHigh morbidity group box 1(HMGB1)とADSC由来のSchwann様細胞に着目した。還元型HMGB1は幹細胞の細胞周期を進行させ組織再生に寄与する可能性が報告されている(PNAS. 2018)。今回、還元型HMGB1がmTORC1シグナルを介してADSCをSchwann様細胞に分化・促進して、これを投与することで、括約筋群の動き・発達にも繋がるとの仮説に基づき、鎖肛を想定した排便機能傷害モデルにおいて、臨床応用を目指した脂肪由来Schwann様細胞投与による神経再生促進および排便機能改善効果を確立する目的で本研究計画を立案した。
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| Outline of Final Research Achievements |
In anorectal malformation, the sphincter muscles are often congenitally poorly formed and developed, making postoperative defecation management difficult. In the present study, we aimed to establish the effects of adipose-derived Schwann-like cells (SLC) administration on nerve regeneration and improvement of defecation function in a defecation injury model of anal-clavicular anus, with the aim of clinical application. In this study, a protocol to induce differentiation of ADSCs into SLCs was established and the effects of SLCs were investigated by administering SLCs after the creation of a defaecal injury rat model. The results are as follows: 1. Differentiation induction from ADSCs to Schwann cells was successfully achieved; 2. Defecation disorder model rats were created; 3. Transplantation of SLCs into the defecation disorder model resulted in improvement of bladder inner pressure and bladder wall thickness.
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| Academic Significance and Societal Importance of the Research Achievements |
鎖肛（直腸肛門奇形）では、先天的に括約筋群の形成・発達が悪い事も多く、特に高位型では直腸肛門形成術を施行しても排便機能が不良な症例が存在し、術後の排便管理に難渋している。鎖肛において骨盤内臓神経再生による排便機能改善効果についての報告はなく、ADSCを用いた骨盤内臓神経再生・排便障害改善が確立され、臨床応用できれば画期的な治療法となる。
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