Yoshioka Toru, Ageyama Naohide, Shibata Hiroaki, Yasu Takanori, Misawa Yoshio, Takeuchi Koichi, Matsui Keiji, Yamamoto Keiji, Terao Keiji, Shimada Kazuyuki, Ikeda Uichi, Ozawa Keiya, Hanazono Yutaka
Center for Molecular Medicine, Department of Internal Medicine, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.
Stem Cells. 2005 Mar;23(3):355-64. doi: 10.1634/stemcells.2004-0200.
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.
啮齿动物和人类临床研究表明,将骨髓干细胞移植到缺血心肌可改善心脏功能。在本研究中,通过结扎左前降支动脉制造食蟹猴急性心肌梗死,并将自体CD34(+)细胞移植到缺血周边区域。为追踪移植细胞在体内的命运,移植前使用慢病毒载体用绿色荧光蛋白(GFP)对CD34(+)细胞进行基因标记(标记效率平均为41%)。与盐水处理组(n = 4)相比,接受细胞移植的组(n = 4)在移植后2周时区域血流和心脏功能得到改善。然而,发现极少有移植细胞来源的GFP阳性细胞整合到血管结构中,并且在修复组织中未检测到GFP阳性心肌细胞。另一方面,发现培养的CD34(+)细胞分泌血管内皮生长因子(VEGF),并且移植后体内区域VEGF水平显著升高。这些结果表明,改善并非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血管生成活性的可能性。
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