2023 Fiscal Year Final Research Report
Characterization of conditioned medium of immortalized human exfoliated deciduous teeth and its therapeutic effect against a pressure ulcer mouse model
| Project/Area Number |
21K09779
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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 56070:Plastic and reconstructive surgery-related
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
善本 隆之 東京医科大学, 医学部, 教授 (80202406)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 乳歯歯髄幹細胞 / 細胞培養上清 / 不死化幹細胞 / 褥瘡モデルマウス |
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| Outline of Final Research Achievements |
In the present study, immortalized stem cell line from human exfoliated deciduous teeth (SHED) was established aiming at implementation of its conditioned medium (CM) in human medicine. The SHED-CM was biochemically analyzed and its inhibitory effect on ulcer formation was investigated using a mouse model of pressure ulcer. Immortalized SHED cells have a high proliferative and cytokine-producing capacity. Intradermal injections of the SHED-CM significantly suppressed a mouse model of pressure ulcer formation caused by ischemia-reperfusion injury induced by sandwiching the dorsal skin between two magnets. The possible mechanisms of action are highly attributed to the promotion of angiogenesis and inhibition of reactive oxygen species generation by hepatocyte growth factor and vascular endothelial cell growth factor in the SHED-CM, which were suggested by using antibody-based immunodepletion experiments and in vitro cell culture systems.
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| Free Research Field |
再生医療
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| Academic Significance and Societal Importance of the Research Achievements |
最近、間葉系幹細胞（MSC）の培養上清（CM）の投与が、細胞フリー療法として、拒絶反応の可能性を懸念することなく、治療効果や安全性も高いため注目されている。そこで、CMの製剤化を考えた場合、無限に安定的に増え同一性の高いCMの調製を可能とする不死化MSCを作製し、それをCMの供給源とすることが一番良いと考えた。高齢化が加速する今日の日本において、褥瘡、いわゆる床すれは、寝たきりの高齢者にはその対応が必須ではあるが、その根本的な治療法や予防法は今のところ存在しない。本研究成果は、この褥瘡などの潰瘍形成に対して、不死化した乳歯歯髄幹細胞のCMの医薬品としての有効性を示唆するものである。
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