Hypoxic preconditioning enhances angiogenic potential of bone marrow cells with aging-related functional impairment

Background: Hypoxic preconditioning of bone marrow cells (BMCs) from young healthy individuals can enhance the cells' therapeutic potential. Considering that the response to hypoxia may differ according to the quality of the cells, we assessed the effect of hypoxic preconditioning on BMCs from aged mice and compared the difference in response between BMCs from aged and young mice. Methods and Results: BMCs from young (3 months) and aged (20-22 months) mice were subjected to hypoxic preconditioning by culture for 24 h in 2% O₂. Compared with BMCs from young mice, those from aged mice showed significantly fewer CD34- or c-kit-positive stem cells, higher expression of p53, and lower telomerase activity. Adhesion, survival and angiogenic potency were also lower in BMCs from aged mice, indicating an aging-related impairment. Hypoxia-preconditioned BMCs from aged mice showed enhanced adhesion, survival, and angiogenic potency with the in vitro assessments, as well as the in vivo implantation into ischemic hindlimbs. All the enhancements by hypoxic preconditioning were comparable between BMCs from aged and young mice, although the angiogenic potential of BMCs with and without hypoxic preconditioning was lower in old mice compared with young mice. Conclusions: Similar responses to hypoxia by BMCs from both aged and young mice suggest that hypoxic preconditioning could be a useful method of enhancing the angiogenic potential of BMCs.