Asialoerythropoietin is a strong modulator of angiogenesis by bone-marrow cells

The angiogenetic effect of asialoerythropoietin (asialoEPO) was investigated in a murine (BALB/c) ischemic hind limb model created by ligating the right femoral artery, and severe ischemia was created by ligating two points on the femoral artery. The mice were allocated to six groups: 1, Control (n = 15), no treatment; 2, BMC (n = 15), Injected with 1 x 10(6) bone marrow cells (BMC); 3, EPO (n = 15), EPO(500 U/kg for 2 weeks); 4, BMC + EPO (n = 15), BMC + erythropoietin (EPO); 5, asialoEPO (n = 15), asialoEPO (500 U/kg for 2 weeks); 6, BMC + asialoEPO (n = 15); BMC + asialoEPO. Blood flow in the ischemic and normal limbs was measured using a Doppler flowmeter on days 7 and 14. Vessel density was evaluated by immunohistochemical staining for Von Willebrand Factor (vWF). In the severe ischemia model, limb survival was investigated. Blood flow was significantly higher in the BMC + asialoEPO group than in the Control, BMC, EPO, BMC + EPO, or asialoEPO group on day 7 (p = .007) and on day 14 (p = .002). Vascular density was also significantly higher in the BMC + asialoEPO (0.067 +/- 0.022) group than in the Control (0.026 +/- 0.007), BMC (0.027 +/- 0.012) EPO (0.029 +/- 0.002), BMC + EPO (0.048 +/- 0.015), and asialoEPO (0.031 +/- 0.001) groups (p = .006). Finally, limb survival at day 14 in the severe ischemia model was significantly better in the BMC + asialoEPO group (83.3%) than in the Control (40.0%), BMC (52.9%), EPO (44.4%), BMC + EPO (64.7%), or asialoEPO (36.4%) group (p = .02). This provides the conclusions that asialoEPO promotes angiogenesis by BMC and that its action is significantly more potent than that of EPO.