Intra-arterial transplantation of adult bone marrow cells restores blood flow and regenerates skeletal muscle in ischemic limbs

Objective: Bone marrow cell therapy promotes angiogenesis, but the cellular fate of bone marrow cells (BMCs) in the absence of immunosuppressant interventions is unclear. We created a model of severe hind limb ischemia to address whether BMCs form new blood vessels or differentiate into other tissues. Methods and Results: After ligating the common femoral artery in ApoE knockout mice, we injected either phosphate buffered saline (PBS) or 5 × 107 adult unfractionated BMCs obtained from green fluorescent protein-positive mice. Laser Doppler imaging of the ischemic limbs revealed that intra-arterial BMCs significantly increased blood flow recovery in ischemic limbs beginning 21 days after surgery and peaking at 27 days (61.8% ± 15% vs. 41.9% ± 13.9%, respectively, for BMCs and PBS, P < .05). The BMCs differentiated into small blood vessels, skeletal myofibers, and supporting membranes, and these changes were associated with increased serum levels of vascular endothelial growth factor (VEGF), fibroblast growt...