Division of Pediatric Cardiology, Department of Pediatrics, Kwandong University College of Medicine, Myongji Hospital Cardiac Center, Seoul, Republic of Korea.
Biochem Biophys Res Commun. 2010 Nov 12;402(2):272-9. doi: 10.1016/j.bbrc.2010.10.013. Epub 2010 Oct 16.
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-C2α). PI3K-C2α overexpression increased PI3K expression and the cell viability of MSCs. Furthermore, levels of survival-related phosphorylation were elevated in PI3K-C2α-MSCs. But, the level of apoptotic proteins downregulated and the number of PI-positive cells decreased in PI3K-C2α-MSCs compared to hypoxic MSCs. Nine rats per group had 1×10(6) cells (20 μl PBS) transplanted after myocardial infarction. One week after transplantation, infarct size and area of fibrosis were reduced in the PI3K-C2α-MSC-transplanted group. The number of TUNEL positive cells declined, while the mean microvessel count per field was higher in the PI3K-C2α-MSC group than the MSC-injected group. Heart function was improved in the PI3K-C2α-MSCs group as assessed using a Millar catheter at 3weeks after transplantation. These findings suggest that overexpression of PI3K-C2α in MSCs can assist cell survival and enhance myocardial regeneration.
间质干细胞（MSC）治疗心肌再生的疗效受到移植到梗死心脏后的干细胞存活率低的限制。为了提高 MSCs 在梗死心脏中的细胞存活率，将 MSCs 基因工程改造以过表达磷酸肌醇-3-激酶 II 类 α（PI3K-C2α）。PI3K-C2α 的过表达增加了 PI3K 的表达和 MSCs 的细胞活力。此外，PI3K-C2α-MSCs 中与存活相关的磷酸化水平升高。然而，与缺氧 MSC 相比，PI3K-C2α-MSCs 中的凋亡蛋白水平下调，PI 阳性细胞数量减少。每组 9 只大鼠在心肌梗死后移植 1×10(6)个细胞（20 μl PBS）。移植后 1 周，PI3K-C2α-MSC 移植组的梗死面积和纤维化面积减少。PI3K-C2α-MSC 组的 TUNEL 阳性细胞数量减少，而每个视野的平均微血管计数高于 MSC 注射组。移植后 3 周，通过 Millar 导管评估，PI3K-C2α-MSCs 组的心功能得到改善。这些发现表明，在 MSCs 中过表达 PI3K-C2α 可以帮助细胞存活并增强心肌再生。
