Effect of exosome derived from iPS cells on wound healing

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K15652
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Plastic surgery
• Research Institution: Nagoya University
• Principal Investigator: Kambe Miki 名古屋大学, 医学部附属病院, 病院助教 (50597862)
• Co-Investigator(Kenkyū-buntansha): 亀井 譲 名古屋大学, 医学系研究科, 教授 (10257678) ; 蛯沢 克己 名古屋大学, 医学部附属病院, 病院助教 (20397459) ; 加藤 竜司 名古屋大学, 創薬科学研究科, 准教授 (50377884) ; 高成 啓介 名古屋大学, 医学系研究科, 講師 (80378190)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: iPSエクソソーム / 創傷治癒

Outline of Final Research Achievements

We investigated the potency of promoting diabetic wound healing by the application of human exosomes derived from human induced pluripotent stem cells. Exosomes derived from iPSCs culture medium (M-Exo) and hiPSCs conditioned medium (hiPS-Exo) were isolated. We evaluated the in vitro effects of hiPSC-Exo on diabetic mouse dermal fibroblasts. PBS, M-Exo, and iPS-Exo were respectively injected subcutaneously around skin defect in a diabetic mouse model, and their effects on wound healing were assessed.hiPS-Exos stimulated the migration of diabetic mouse dermal fibroblasts in vitro, but does not stimulated its proliferation. Injected hiPS-Exo to wound sites resulted in accelerated wound closure. Our findings suggest that hiPS-Exo enhances diabetic skin wound healing by accelerating fibroblast migration. hiPS-Exo might become a therapeutic option for diabetic ulcer.

Free Research Field

創傷治癒

Academic Significance and Societal Importance of the Research Achievements

iPS細胞は胚組織を使用しない万能細胞として注目を集めているものの、奇形種形成の懸念があり、広く臨床応用するには懸念が残っている。近年、幹細胞培養上清の有用性がさまざまな疾患モデルで報告され、その治癒メカニズムの一因として、RNAやタンパク質を輸送する微小胞「エクソソーム」の関与が指摘されている。本研究の結果、iPS細胞由来エクソソームが糖尿病性潰瘍の治癒を促進する事が示された。これにより、罹患数の多い糖尿病性潰瘍に対する新たな治療法開発の可能性が示唆され、社会的にも意義があると考える。