Abstract 9198: Hypoxic Preconditioning Enhances the Angiogenic and Therapeutic Potential of Bone Marrow Cells with Age-Related Functional Impairment

Abstract

Background: Previous studies have demonstrated that ex vivo hypoxic preconditioning (HP) of bone marrow cells (BMCs) can enhance their potency for inducing therapeutic angiogenesis, but experiments have all used cells from young healthy individuals. Considering that the response to hypoxia may differ depending on the quality of cells and that cell-based therapy were usually conducted in patients with advanced age, we investigated whether there was a difference in the response to HP between BMCs from old and young mice. Methods and Results: BMCs were collected from young (3 months) and old (20-22 months) C57BL/6 mice, and subjected to HP by incubating in 2% O 2 for 24 hour. Adhesion, survival and angiogenic potency were significantly worse (all P<0.05) in BMCs from old mice than in those from young mice, indicating an age-related functional impairment of the BMCs. Agreed well with previous studies using cells from young healthy mice, HP of BMCs from old mice resulted in a significant increase in adhesion (P<0.01) and survival (P<0.01). The hypoxia-preconditioned BMCs also had a significant increase in angiogenic potency, including the production of VEGF (P<0.05) and endothelial differentiation (P<0.05). All of these enhancements by HP were comparable between BMCs from old and young mice. On intramuscular implantation of BMCs into the ischemic hindlimbs of old mice, microvessel density and blood flow (Fig A) in the ischemic hindlimbs 14 days after treatment was significantly increased in the mice implanted with the hypoxia-preconditioned BMCs from old mice than in those implanted with the freshly isolated or the normoxia-cultured BMCs from old mice; a similar preconditioning effect was observed in BMCs from young mice (Fig B). Conclusion: HP-induced enhancement of angiogenic potential of BMCs from old mice follows the same trend as that of BMCs from young mice, suggesting that HP could be a useful method of enhancing the potential of BMCs for therapeutic angiogenesis.