Table 1.
Hypoxia and the potential mechanisms for preconditioning on MSCs
| O2 content | Effect | Mechanism | Reference |
|---|---|---|---|
| 0.5% | Counteracts the deficiency of adipose‐derived MSCs from older donors and highly improves their differentiation capacity | Acts as a protective factor | 23 |
| 1% | Prevents the apoptosis of MSCs | Increases the secretion of angiogenic factors, VEGF and basic fibroblast growth factor (BFGF) in MSCs | 36 |
| 1% | Decreases the sensitivity of MSCs to the ischaemic microenvironment without changing their biological behaviour, immunophenotype or karyotype | Increases the metabolic activity and decreases the caspase‐3/7 activity and lactate dehydrogenase release of MSCs | 37 |
| 2% | Decreases tumorigenic potential of MSCs | Down‐regulates the expression levels of tumour‐suppressor genes and TERT and the suboptimal double‐stranded DNA breaks in MSCs | 17 |
| 3% | Improves the genetic stability and chromosome stability and guarantees the safety of MSCs | Decreases the incidence of aneuploidy in MSCs | 38 |
| 5% | Enhances the clonogenic potential and proliferation rate of MSCs | Up‐regulates the vascular endothelial growth factor (VEGF) secretion in MSCs | 35 |
| 5% | Exerts no effect on the phenotype or differentiation ability of MSCs but significantly enhances the autophagy progress | Increases the expression of HIF‐1α and activates the AMPK/mTOR signalling pathway | 39 |
| 0.1–0.3% | Promotes neurogenesis and neurological functional recovery | Promotes the secretion of various growth factors including brain‐derived neurotrophic factor (BDNF), glial cell line‐derived neurotrophic factor (GDNF) and VEGF | 40 |
| 0.5% | Improves the motor and cognitive function of the animal models | Promotes the secretion of growth factors including hepatocyte growth factor (HGF) and VEGF | 42 |
| 0.5% | Suppresses microglia activity in the brain and promotes locomotion recovery | Up‐regulates the expression levels of HIF‐1α, the VEGF receptor, erythropoietin (EPO), the EPO receptor, stromal‐derived factor‐1 (SDF‐1) and CXC chemokine receptor 4 (CXCR4) but decreases the release of pro‐inflammatory cytokines | 43 |
| 1% | Promotes liver regeneration in massive hepatectomy models | Increases the expression of cyclin D1 and VEGF, enhances the proliferation of hepatocytes and increases the liver weight/bodyweight ratio | 41 |
| 1% | Improves the intracavernosal pressure and erectile function in diabetes models | Up‐regulates the release of angiogenesis‐ and neuroprotection‐related factors including VEGF, the VEGF receptor, angiotensin, BFGF, BDNF, GDNF, SDF‐1 and CXCR4; up‐regulates the expression levels of NO synthases, endothelial markers and smooth muscle markers | 45 |
| 1.5% | Compensates the loss of lung functions in idiopathic pulmonary fibrosis models | Improves the proliferation, migration, angiogenesis, antioxidant, antiapoptotic and antifibrotic properties of implanted MSCs | 46 |
| 1.5% | Guarantees the safety of cell transplantation | Inhibits the malignant transformation of MSCs | 47 |
| 1–7% | Repairs the injury in a murine hindlimb ischaemia model | Activates the HIF‐1α/GRP78/Akt signal axis | 48 |
| 2% | Promotes the recovery of the ischaemic tissue | Improves the expression of prion protein (PrPC), activates PrPC‐dependent JAK2 and STAT3 signalling pathways, and then up‐regulates the activity of superoxide dismutase and catalase | 49 |
| 2% | Inhibits the rabbit femoral head osteonecrosis | Increases the angiogenesis function and decreases the tissue apoptosis | 50 |
| 5% | Facilitates revascularization in diabetic lower limb ischaemia (DLLI) | Increases the expression levels of angiogenin, matrix metallopeptidase (MMP)‐9, VEGF‐1α and HIF‐1α and activates the p‐AKT signalling pathway | 51 |