Differential bone marrow stem cell mobilization by G-CSF injection or arterial ligation in baboons.

ABSTRACT

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.