Regeneration of infarcted myocardium with resveratrol-modified cardiac stem cells.
Regeneration of infarcted myocardium with resveratrol-modified cardiac stem cells.
复制标题
用白藜芦醇修饰的心脏干细胞再生梗塞心肌的再生。
DOI：
10.1111/j.1582-4934.2011.01281.x
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发表时间：
2012-01
影响因子：
5.3
通讯作者：
Das DK
中科院分区：
文献类型：
--
作者：
Gorbunov N;Petrovski G;Gurusamy N;Ray D;Kim DH;Das DK
干细胞治疗的主要问题包括干细胞移植后的存活率和植入效率。事实上，绝大多数宿主输注的细胞不能存活超过24-72小时。为了增加植入的心脏干细胞在宿主中的存活和植入，我们开发了一种用白藜芦醇处理这些细胞的技术，并在左前降支（LAD）闭塞的大鼠模型中进行了测试。从大鼠心脏分离并稳定转染EGFP的多能克隆性心脏干细胞用2.5 μM白藜芦醇预处理60 min。一周后，通过核因子E2相关因子2（Nrf 2）和氧化还原效应因子1（Ref-1）的表达增强，证实了白藜芦醇处理的大鼠心脏中的心脏还原环境。干细胞治疗后的M型超声心动图显示，治疗组和对照组7天后的心功能（左心室射血分数、缩短分数和心输出量）均有所改善，但只有白藜芦醇修饰的干细胞组在1、2和4个月结束时显示心功能改善。心脏功能的改善伴随着增强的干细胞存活和植入，如通过细胞增殖标志物Ki 67的表达和干细胞向心肌再生的分化所证明的，如通过白藜芦醇处理的干细胞组中LAD闭塞后长达4个月的EGFP的表达所证明的。基质细胞衍生因子和肌球蛋白的表达最终证明了干细胞在梗死心肌中的归巢，其再生导致心脏功能的改善。
The major problem in stem cell therapy includes viability and engraftment efficacy of stem cells after transplantation. Indeed, the vast majority of host-transfused cells do not survive beyond 24–72 hrs. To increase the survival and engraftment of implanted cardiac stem cells in the host, we developed a technique of treating these cells with resveratrol, and tested it in a rat model of left anterior descending (LAD) occlusion. Multi-potent clonogenic cardiac stem cells isolated from rat heart and stably transfected with EGFP were pre-treated with 2.5 μM resveratrol for 60 min. Rats were anaesthetized, hearts opened and the LAD occluded to induce heart attack. One week later, the cardiac reduced environment was confirmed in resveratrol treated rat hearts by the enhanced expression of nuclear factor-E2-related factor-2 (Nrf2) and redox effector factor-1 (Ref-1). M-mode echocardiography after stem cell therapy, showed improvement in cardiac function (left ventricular ejection fraction, fractional shortening and cardiac output) in both, the treated and control group after 7 days, but only resveratrol-modified stem cell group revealed improvement in cardiac function at the end of 1, 2 and 4 months time. The improvement of cardiac function was accompanied by enhanced stem cell survival and engraftment as demonstrated by the expression of cell proliferation marker Ki67 and differentiation of stem cells towards the regeneration of the myocardium as demonstrated by the expression of EGFP up to 4 months after LAD occlusion in the resveratrol-treated stem cell group. Expression of stromal cell-derived factor and myosin conclusively demonstrated homing of stem cells in the infarcted myocardium, its regeneration leading to improvement of cardiac function.
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