Abstract
To achieve the full therapeutic potential of implanted adipose stem cells (ASCs) in vivo, it is crucial to improve the viability and pro-angiogenic properties of the stem cells. Here, we first simulated the conditions of ischemia and hypoxia using the in vitro oxygen-glucose deprivation (OGD) model and confirmed that hypoxic preconditioning of ASCs could provide improved protection against OGD and enhance ASC viability. Second, we assessed the effect of hypoxic preconditioning on pro-angiogenic potential of ASCs, with a particular focus on the role of vascular endothelial growth factor-A (VEGF-A) and stromal derived factor-1a (SDF-1a) paracrine activity in mediating angiogenesis. We found that the conditioned medium of ASCs (ASCCM) with hypoxic preconditioning enhanced angiogenesis by a series of angiogenesis assay models in vivo and in vitro through the upregulation of and a synergistic effect between VEGF-A and SDF-1a. Finally, to investigate the possible downstream mechanisms of VEGF/VEGFR2 and SDF-1a/CXCR4 axes-driven angiogenesis, we evaluated relevant protein kinases involved the signal transduction pathway of angiogenesis and showed that VEGF/VEGFR2 and SDF-1a/CXCR4 axes may synergistically promote angiogenesis by activating Akt. Collectively, our findings demonstrate that hypoxic preconditioning may constitute a promising strategy to enhance cellular viability and angiogenesis of transplanted ASCs, therein improving the success rate of stem cell-based therapies in tissue engineering.
Highlights
Recent developments in stem cell-based therapy have received considerable attention and produced promising results for tissue repair and functional tissue reconstruction after trauma
Hypoxia Enhances the Viability of adipose stem cells (ASCs) Exposed to oxygenglucose deprivation (OGD)
The caspase 3 activity assay showed that ASCs with hypoxic preconditioning(at 2% O2) were protected from OGD-induced cellular apoptosis (Figure 1E)
Summary
Recent developments in stem cell-based therapy have received considerable attention and produced promising results for tissue repair and functional tissue reconstruction after trauma. In the early days of tissue engineering, stem cells were used to promote tissue repair via migration to the damage sites and subsequent differentiation into tissue-specific cells (Hanson et al, 2010). This approach limited the potential benefits of stem cell-based therapy, because the viability of the implanted cells was strongly affected by microenvironment conditions in the implantation area. In the past few years, gene modification methods had been used to strengthen the original genotype Such approaches disrupt genome stability and can cause unpredictable gene mutations, which reduce their potential use in clinical applications on safety grounds (Guo, 2017). Nowadays, preconditioning (non-genetic methods), which improve the viability of and pro-angiogenic factor release by stem cells, attracts considerable attention and considered to be safe and efficient for clinical use (Paquet et al, 2015)
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