Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA.
Southwest National Primate Research Center, San Antonio, TX, USA.
J Cell Mol Med. 2009 Aug;13(8B):1896-1906. doi: 10.1111/j.1582-4934.2008.00405.x.
Bone marrow stem cells (BMSCs) are mobilized in response to ischemic attacks, e.g. myocardial infarction, to repair the damage, or by cytokines, e.g. granulocyte colony-stimulating factor (G-CSF), which is used to harvest BMSCs for autologous transplantation. In order to optimize BMSC mobilization strategy for cardiovascular repair, we investigated whether BMSCs mobilized by G-CSF share the same subtype profile as that by ischemia in a non-human primate model. We subjected five baboons to subcutaneous G-CSF injection and five baboons to femoral artery ligation. Blood BMSCs were measured by surface antigens; functional differentiation to endothelial cells (ECs) was assessed by colony-forming capacity, expression of mature EC antigens and tube-like formation. The number of circulating CD34+/CD45RA- cells spiked on day 3 post-stimulation in both groups. While the number of CD34+ cells released by artery ligation was 2-fold lower by comparison with the number released by G-CSF administration, significantly more CD133+/KDR+/CXCR4+/CD31+ cells were detected in the baboons that underwent artery ligation. After culture in endothelial growth medium, mononuclear cells from baboons with artery ligation formed more EC colonies and more capillary-like tubes (P < 0.05), expressed higher vWF and phagocytosed more Dil-Ac-LDL (P < 0.05). While G-CSF and artery ligation can mobilize BMSCs capable of differentiating into ECs, BMSCs mobilized by the artery ligation simulating in vivo ischemic attacks have higher potential for vascular differentiation. Our findings demonstrate that different mobilization forces release different sets of BMSCs that may have different capacity for cardiovascular differentiation.
骨髓干细胞（BMSCs）在缺血性攻击（如心肌梗死）时被动员以修复损伤，或者通过细胞因子（如粒细胞集落刺激因子（G-CSF））动员以收获 BMSCs 进行自体移植。为了优化用于心血管修复的 BMSC 动员策略，我们研究了 G-CSF 动员的 BMSCs 是否与非人类灵长类动物模型中的缺血具有相同的亚型特征。我们让五头狨猴接受皮下 G-CSF 注射，让五头狨猴接受股动脉结扎。通过表面抗原测量血液 BMSCs；通过集落形成能力、成熟 EC 抗原表达和管状形成评估向内皮细胞（ECs）的功能分化。两组在刺激后第 3 天循环 CD34+/CD45RA-细胞数量都有所增加。虽然通过动脉结扎释放的 CD34+细胞数量比通过 G-CSF 给药释放的数量低 2 倍，但在接受动脉结扎的狨猴中检测到更多的 CD133+/KDR+/CXCR4+/CD31+细胞。在内皮生长培养基中培养后，来自接受动脉结扎的狨猴的单核细胞形成更多的 EC 集落和更多的毛细血管样管（P < 0.05），表达更高的 vWF 并吞噬更多的 Dil-Ac-LDL（P < 0.05）。虽然 G-CSF 和动脉结扎都可以动员能够分化为 EC 的 BMSCs，但模拟体内缺血性攻击的动脉结扎动员的 BMSCs 具有更高的血管分化潜力。我们的研究结果表明，不同的动员力量释放不同的 BMSC 集，这些 BMSC 可能具有不同的心血管分化能力。
