| Project/Area Number |
20K18447
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56070:Plastic and reconstructive surgery-related
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| Research Institution | Juntendo University |
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Principal Investigator |
Miho Tobita 順天堂大学, 医学部, 助手 (30838686)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 表皮幹細胞 / 糖尿病性潰瘍 / 創傷治癒 / 皮膚 / 糖尿病 / 再生医療 |
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| Outline of Research at the Start |
近年、表皮幹細胞を可視化させる遺伝子組み換えマウスを用いた実験では、標識した表皮幹細胞が損傷した皮膚へ娘細胞を供給し、潰瘍部位の再上皮化に関与することが注目されている。しかし、糖尿病性潰瘍の皮膚で表皮幹細胞はどのように変化が起こり、難治性潰瘍に至るのは模索の状態である。これら学術的背景のもと、申請者は糖尿病性潰瘍の皮膚では表皮幹細胞の供給が抑制され、難治性潰瘍に繋がると仮説をたてた。仮説証明のため、糖尿病潰瘍モデルマウスを用いて、損傷皮膚再生する時の表皮幹細胞の拳動を追跡し、表皮再生制御の機序を明らかにする。
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| Outline of Final Research Achievements |
Diabetic ulcers are intractable ulcers and the mechanism of skin regeneration is also disrupted, and epidermal stem cells are important in this skin regeneration process, and it has already been reported that epidermal stem cells present in hair follicles are the source of epidermal cells. Therefore, we investigated the amount and function of epidermal stem cells in diabetic ulcer skin and worked to elucidate the mechanism of delayed ulcer skin reconstruction.
Tissue analysis of the epidermis of human diabetic ulcer skin revealed that epidermal stem cells were almost absent in the epidermis. Furthermore, genetic analysis showed that epidermal stem cells derived from diabetic ulcer skin had increased DNA damage and apoptosis-related gene expression compared to normal skin-derived epidermal stem cells. It was found that diabetic epidermal stem cells have been declining in number and function.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病性潰瘍の治療のため、難治性潰瘍皮膚における表皮幹細胞の動態を探求することで、表皮再生の制御因子を同定し、表皮幹細胞の機能改善法を樹立する。特定因子が同定されれば、難治性皮膚に生じている表皮幹細胞の量と質の低下を回復させる試薬の開発や細胞移植治療へ発展することが期待される。既存治療では治癒困難な難治性皮膚潰瘍に対する新しい治療法開発への橋渡しとなると考案する。
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