Overexpression of phosphoinositide-3-kinase class II alpha enhances mesenchymal stem cell survival in infarcted myocardium

被引：19
作者：
Eun, Lucy Youngmin [2 ]
Song, Byeong-Wook [1 ,3 ]
Cha, Min-Ji [1 ,3 ]
Song, Heesang [1 ]
Kim, Il-Kwon [1 ,3 ]
Choi, Eunmi [1 ,5 ]
Chang, Woochul [1 ]
Lim, Soyeon [1 ]
Choi, Eun Ju [1 ,3 ]
Ham, Onju [1 ,3 ]
Lee, Se-Yeon [1 ,3 ]
Byun, Ki Hyun [2 ]
Jang, Yangsoo [1 ,3 ,4 ]
Hwang, Ki-Chul [1 ,3 ,5 ]
机构：
[1] Yonsei Univ, Coll Med, Cardiovasc Res Inst, Seoul 120752, South Korea
[2] Kwandong Univ Coll Med, Myongji Hosp Cardiac Ctr, Dept Pediat, Div Pediat Cardiol, Seoul, South Korea
[3] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul 120752, South Korea
[4] Yonsei Univ, Coll Med, Div Cardiol, Seoul 120752, South Korea
[5] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul 120752, South Korea
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2010年 / 402卷 / 02期
关键词：
Cardiac regeneration; Lentivirus; Mesenchymal stem cells; Phosphoinositide-3-kinase class II alpha; Survival; IMPROVES CARDIAC-FUNCTION; ISCHEMIC-MYOCARDIUM; REPAIR; DEATH; TRANSPLANTATION; 3-KINASE; GROWTH; HEART; EXPRESSION; STRATEGIES;
D O I：
10.1016/j.bbrc.2010.10.013
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The efficacy of mesenchymal stem cell (MSC) therapy for myocardial regeneration is limited by the poor survival of stem cells after transplantation into the infarcted heart. To improve the cell survival of MSCs in the infarcted heart, MSCs were genetically engineered to overexpress phosphoinositide-3-kinase class II alpha (PI3K-C2 alpha). PI3K-C2 alpha overexpression increased PI3K expression and the cell viability of MSCs. Furthermore, levels of survival-related phosphorylation were elevated in PI3K-C2 alpha-MSC5. But, the level of apoptotic proteins downregulated and the number of PI-positive cells decreased in PI3K-C2a-MSC5 compared to hypoxic MSCs. Nine rats per group had 1 x 10(6) cells (20 mu I PBS) transplanted after myocardial infarction. One week after transplantation, infarct size and area of fibrosis were reduced in the PI3K-C2 alpha-MSC-transplanted group. The number of TUNEL positive cells declined, while the mean microvessel count per field was higher in the PI3K-C2 alpha-MSC group than the MSC-injected group. Heart function was improved in the PI3K-C2 alpha-MSC5 group as assessed using a Millar catheter at 3 weeks after transplantation. These findings suggest that overexpression of PI3K-C2a in MSCs can assist cell survival and enhance myocardial regeneration. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码：272 / 279
页数：8
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