Background: We previously showed that exposure of cultured bone marrow stem cells (BMSC) to hypoxia or anoxia increases levels of hepatocyte growth factor, vascular endothelial growth factor and fibroblast growth factor in the culture medium. We also showed that multiple intravenous administration of this hypoxia/anoxia conditioned BMSC culture medium (BMSC-cm) alone (without the stem cells) results in chronic improvement of LV ejection fraction and prevention of progressive LV dilation in dogs with chronic heart failure (HF). This study examined protein levels of insulin-like growth factor-1 (IGF-1) and angiopoietin-1 (Ang-1) in BMSC-cm. IGF-1 is a potent activator of the AKT signaling pathway, a stimulator of cell growth and proliferation and potent inhibitor of apoptosis. Ang-1 promotes angiogenesis and also counteracts cell death by apoptosis. Methods: BMSCs were obtained from dogs and cultured using Iscoves modified Dulbecco medium. Protein level of IGF-1 and Ang-1 were measured in the medium from cultured BMSCs exposed to anoxia (95% nitrogen and 5% carbon dioxide) for 72 hours and in the medium from cultured BMSCs exposed to normoxia (95% room air and 5% carbon dioxide). Protein levels were measured using commercially available enzyme-linked immunosorbent assay (ELISA). Results: Levels of IGF-1 in the cell free medium increased from an average of 3.59 ± 0.06 ng/ml under normoxic conditions to 5.33 ± 0.14 ng/ml under anoxic conditions (p<0.05). Similarly, levels of Ang-1 in the cell free medium increased from an average of 895 ± 30 pg/ml under normoxic conditions to 2,584 ± 91 pg/ml under anoxic conditions (p<0.05). Conclusions: Exposure of BMSCs to anoxic conditions can markedly increase protein levels of IGF-1 and Ang-1 in the cell free culture medium. Given that IGF-1 and Ang-1 possess cell proliferative effects, angiogenic effects and anti-apoptotic effects, the results provide a potential explanation for the improved LV function and prevention of LV dilation seen when dogs with HF were treated with BMSC-cm.