The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
J Cell Mol Med. 2012 Jan;16(1):174-84. doi: 10.1111/j.1582-4934.2011.01281.x.
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.
干细胞治疗的主要问题包括移植后干细胞的活力和植入效果。实际上，绝大多数输入的宿主细胞在 24-72 小时内无法存活。为了提高宿主中植入心脏干细胞的存活率和植入效果，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。从大鼠心脏中分离出的多能克隆心脏干细胞，并稳定转染 EGFP，用 2.5μM 白藜芦醇预处理 60 分钟。大鼠麻醉后，心脏开放并结扎 LAD 以诱导心肌梗死。一周后，通过核因子-E2 相关因子-2（Nrf2）和氧化还原效应因子-1（Ref-1）的增强表达，证实了白藜芦醇处理的大鼠心脏中心脏还原环境的存在。干细胞治疗后的 M 模式超声心动图显示，在 7 天后，治疗组和对照组的心脏功能（左心室射血分数、分数缩短和心输出量）均有所改善，但只有白藜芦醇修饰的干细胞组在 1、2 和 4 个月时显示出心脏功能的改善。心脏功能的改善伴随着干细胞的存活和植入的增强，这表现为细胞增殖标志物 Ki67 的表达，以及干细胞向心肌再生的分化，这在 LAD 闭塞后 4 个月的白藜芦醇处理的干细胞组中得到了证明。基质细胞衍生因子和肌球蛋白的表达明确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。
