Development of MSC-derived extracellular vesicle for clinical application

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06964
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: University of Tsukuba
• Principal Investigator: Ohneda Osamu 筑波大学, 医学医療系, 教授 (30311872)
• Co-Investigator(Kenkyū-buntansha): VUONG CAT・KHANH 筑波大学, 医学医療系, 助教 (20816102) ; 山下 年晴 筑波大学, 医学医療系, 助教 (50400677)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 間葉系幹細胞 / 2型糖尿病 / 老化 / 細胞外小胞

Outline of Final Research Achievements

To elucidate functional abnormalities of MSCs derived from patients with diseases (type 2 diabetes) and functional decline of MSCs due to aging at the molecular level, this study was performed. The following studies were conducted using extracellular vesicles (EVs): 1) dEVs derived from dAT-MSCs collected from adipose tissue of patients with type 2 DM were compared with EVs derived from nAT-MSCs of healthy subjects; 2) administration of dEVs to nAT-MSCs did not alter proliferative ability but significantly increased adipogenic differentiation, and 3) the function of hEVs was significantly enhanced in patients with type 2 DM.
Elderly AT-MSCs; eAT-MSCs showed decreased proliferative and differentiation capacity as well as wound healing ability compared to infant AT-MSCs; iAT-MSCs. ROS expression was significantly upregulated in eAT-MSCs compared to i-AT-MSCs, and the increase in ROS was attributed to the decreased expression of Sirtuin-1, a senescence suppression factor.

Free Research Field

再生医学

Academic Significance and Societal Importance of the Research Achievements

Transformed extracellular vesicles with high angiogenic ability as therapeutics of distal ischemic tissues. Front. Cell Dev. Biol.,2022. PMID: 36120585
上記論文を発表することにより、機能性幹細胞から単離された細胞外小胞EVが効果的に標的細胞の性質をトランスフォームすることが可能であることを明らかにした点は、社会的意義が高いものと思われる。