Cellular cardiomyoplasty:: Improvement of left ventricular function correlates with the release of cardioactive cytokines
Cellular cardiomyoplasty:: Improvement of left ventricular function correlates with the release of cardioactive cytokines
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DOI：
10.1634/stemcells.2006-0374
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发表时间：
2007-01-01
期刊：
影响因子：
5.2
通讯作者：
Braun, Thomas
中科院分区：
文献类型：
--
作者：
Ebelt, Henning;Jungblut, Mirco;Braun, Thomas
越来越多的研究报告称，将所谓的心脏干细胞移植到心肌梗死后患病的心脏中会产生有益的效果。然而，移植细胞可能有助于促进心肌组织修复的机制尚不清楚，可能涉及与移植细胞向心肌细胞分化不同的过程。我们通过超声心动图随访和组织学分析比较了骨骼肌成肌细胞(不能形成新的心肌细胞)和胚胎干细胞来源的心肌细胞植入梗死小鼠心脏后的作用，并将这些作用与心脏活性细胞因子的释放有关。我们发现，这两种细胞类型都导致了左心室功能的长期改善和组织结构的改善。由于在移植后28天，梗塞心脏中没有相关数量的成肌细胞来源的细胞，我们研究了移植细胞在移植到梗塞心脏前后细胞因子的释放。ESC来源的心肌细胞和成肌细胞分泌大量的IL-1α、IL-6、肿瘤坏死因子-β和抑癌素M，有力地支持了培养的心肌细胞的存活和蛋白质合成。我们推测，成肌细胞和心肌细胞移植对心脏功能和形态的有益影响仅部分(如果有的话)依赖于移植细胞与心肌的整合，但确实依赖于心脏活性细胞因子的复杂混合物的释放。
A growing number of studies are reporting beneficial effects of the transplantation of alleged cardiac stem cells into diseased hearts after myocardial infarction. However, the mechanisms by which transplanted cells might help to promote repair of cardiac tissue are not understood and might involve processes different from the differentiation of transplanted cells into cardiomyocytes. We have compared the effects exerted by skeletal myoblasts (which are not able to form new cardiomyocytes) and ESC-derived cardiomyocytes after implantation into infarcted mouse hearts by echocardiographic follow-up and histological analysis and related these effects to the release of cardioactive cytokines. We found that both cell types led to a long-lasting improvement of left ventricle function and to an improvement of tissue architecture. Since no relevant amounts of myoblast-derived cells were present in infarcted hearts 28 days after transplantation, we investigated the release of cytokines from implanted cells both before and after transplantation into infarcted hearts. ESC-derived cardiomyocytes and myoblasts secreted substantial amounts of interleukin (IL)-1 alpha, IL-6, tumor necrosis factor-beta, and oncostatin M, which strongly supported survival and protein synthesis of cultured cardiomyocytes. We postulate that the beneficial effects of the transplantation of myoblasts and cardiomyocytes on heart function and morphology only partially (if at all) depend on the integration of transplanted cells into the myocardium but do depend on the release of a complex blend of cardioactive cytokines.