| Project/Area Number |
16K08609
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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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| Research Field |
Pathological medical chemistry
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| Research Institution | University of Tsukuba |
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Principal Investigator |
OHNEDA OSAMU 筑波大学, 医学医療系, 教授 (30311872)
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| Co-Investigator(Kenkyū-buntansha) |
山下 年晴 筑波大学, 医学医療系, 助教 (50400677)
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| Research Collaborator |
Hiramatsu Yuji
Hamada Hiromi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 間葉系幹細胞 / 糖尿病 / 創傷治癒 / マイクロベシクル / 機能性幹細胞 / 移植・再生医療 |
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| Outline of Final Research Achievements |
Adipose tissue has been a main focus for many studies aiming to elucidate the molecular mechanism of type 2 diabetes mellitus and its complications. Adipose tissue-derived MSCs (AT-MSCs) are easily isolated and used for auto transplantation. However, the distinctive characteristics of AT-MSCs from diabetic donors (dAT-MSCs) are still unclear. In this study, I demonstrate that dAT-MSCs have impaired wound healing ability, as shown through tissue analysis of an ischemic flap mouse model. Notably, dAT-MSCs exhibited impaired cell adhesion. I found the transcription factors, early growth response factor-1 (EGR-1) and hypoxic inducible factor-2α (HIF-2α), were highly expressed in dAT-MSCs under hypoxic conditions. Of note, the target genes regulated by these transcription factors, including growth factors and adhesion molecules were significantly upregulated in dAT-MSCs as compared with nAT-MSCs. Knockdown of EGR-1 can restore the characteristic of dAT-MSCs and wound healing ability.
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| Academic Significance and Societal Importance of the Research Achievements |
当該研究により、糖尿病患者さんに対し自己の幹細胞を用いた治療を行う際に、その幹細胞自体が正常に機能しないことにから、何らかの方法を用いて正常に作用するように幹細胞を再機能化することが求められることが明らかとなった。その一つの手段として、健常者由来間葉系幹細胞から放出されるマイクロベシクルが大きな役割を果たすことを明らかにした。患者さんにおいて自家幹細胞移植を行う際に、各疾患に応じた幹細胞治療法に基づいて行う必要があることを示唆している点で社会的意義は大きい。今後、マイクロベシクルを用いた幹細胞加工法が確立し、機能性幹細胞治療法が大きく発展することが期待できる点において学術的意義は大きい。
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