| 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
|
| Project Status |
Completed (Fiscal Year 2023)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
|
|---|
| Keywords | 間葉系幹細胞 / 2型糖尿病 / 老化 / 細胞外小胞 / 細胞小胞 / ２型糖尿病 / 若返り |
|---|
| Outline of Research at the Start |
間葉系幹細胞(MSC)が幹細胞治療において，汎用性の高い細胞ソースとして使用できるようにするために機能的に優れたMSCを単離できるヒト由来組織を同定し，かつ疾患を有する患者由来MSCの機能異常及び老化によるMSC機能低下を分子レベル で解明し, その機能を補完するための方法を確立する.その一つの手段として，細胞が自ら細胞外に放出する細胞外小胞(EV)が挙げられる．標的とするMSCは，以下の２つである；１）2型糖尿病由来MSC、２）高齢者由来MSC．これら標的とするMSCが機能回復するメカニズムを明らかにすべく，異なる組織由来EVあるいは異なる培養条件下で放出されるEVに対して解析を行う．
|
| 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.
|
| 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。
|
