Repair of infarcted myocardium mediated by transplanted bone marrow-derived CD34+ stem cells in a nonhuman primate model
Repair of infarcted myocardium mediated by transplanted bone marrow-derived CD34+ stem cells in a nonhuman primate model
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DOI：
10.1634/stemcells.2004-0200
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发表时间：
2005-03-01
期刊：
影响因子：
5.2
通讯作者：
Hanazono, Y
中科院分区：
文献类型：
--
作者：
Yoshioka, T;Ageyama, N;Hanazono, Y
啮齿动物和人类的临床研究表明，将骨髓干细胞移植到缺血心肌可以改善心功能。本研究通过结扎猕猴左前降支建立急性心肌梗死模型，并将自体CD34(+)细胞移植到缺血区。为了跟踪移植细胞在体内的命运，移植前使用慢病毒载体对CD34(+)细胞进行绿色荧光蛋白(GFP)基因标记(标记效率平均为41%)。移植后2周，接受细胞组(n=4)与生理盐水组(n=4)相比，局部血流量和心功能均有改善。然而，很少发现移植细胞来源的GFP阳性细胞整合到血管结构中，修复后的组织中未检测到GFP阳性心肌细胞。另一方面，培养的CD34(+)细胞可分泌血管内皮生长因子(VEGF)，移植后体内局部VEGF水平显著升高。这些结果表明，这种改善不是移植细胞来源的内皮细胞或心肌细胞生成的结果；并增加了移植细胞分泌的血管生成细胞因子增强内源性细胞的血管生成活性的可能性。
Rodent and human clinical studies have shown that transplantation of bone marrow stem cells to the ischemic myocardium results in improved cardiac function. In this study, cynomolgus monkey acute myocardial infarction was generated by ligating the left anterior descending artery, and autologous CD34(+) cells were transplanted to the peri-ischemic zone. To track the in vivo fate of transplanted cells, CD34(+) cells were genetically marked with green fluorescent protein (GFP) using a lentivirus vector before transplantation (marking efficiency, 41% on average). The group receiving cells (n = 4) demonstrated improved regional blood flow and cardiac function compared with the saline-treated group (n = 4) at 2 weeks after transplant. However, very few transplanted cell-derived, GFP-positive cells were found incorporated into the vascular structure, and GFP-positive cardiomyocytes were not detected in the repaired tissue. On the other hand, cultured CD34(+) cells were found to secrete vascular endothelial growth factor (VEGF), and the in vivo regional VEGF levels showed a significant increase after the transplantation. These results suggest that the improvement is not the result of generation of transplanted cell-derived endothelial cells or cardiomyocytes; and raise the possibility that angiogenic cytokines secreted from transplanted cells potentiate angiogenic activity of endogenous cells.