Table 1. Summary of studies that measured the effects of hypoxic preconditioning on cellular proliferation and angiogenic capacity.
| Author | Cells | Type of study | Number of cells seeded | Hypoxic model | Results |
|---|---|---|---|---|---|
| Pilgaard et al. [16], 2009 Denmark |
hADSC | In-vitro | 12 rows in a 96-well culture plate to a density of 1000 to 0.5 cells per well. |
XVivo hypoxic workbench/ Ambient, 15%, 10%, 5%, 1% O2). |
• 1% and 5 oxygen may inhibit cell proliferation • Clonogenic precursor cells were preserved • Angiogenic factors were identified in hypoxic conditions |
| Weijers et al. [17], 2011 The netherlands |
hADSC | In-vitro | 3×104 cells/cm2 | Hypoxic workstation, CO2- and O2-controlled, humidifier. 20% O2, 5% CO2, or 1% O2, 5% CO2 | • hADSC have increased proliferation in 1% O2
• Reduced cell aging and preservation of stemness in low O2% |
| Valorani et al. [18], 2012 United Kingdom |
hADSC | In-vitro | 1×104 cells/cm2 | Hypoxia workstation (21% O2) or (2% O2) with 5% CO2 | • Increased hADSC expansion and viability in low O2%, • Decrease in apoptosis and necrosis in low O2% |
| Barros et al. [23], 2013 France |
hADSC | In-vitro In-vivo | 4000 cell/cm2 1×106 cell/cm2 | Hypoxic incubator at 0.5% O2 or 21% O2 for 24 h | • hADSC enhanced in-vivo neovascularization • Age of the donor decreased angiogenic benefits •Hypoxic preconditioning reversed the adverse effect of aging |
| Liu et al. [19], 2013 China |
hADSC | In-vitro | 1500 cells were seeded in a 96-well plate | Tri-gas incubator containing 5% CO2, 1% O2, for 48 h. | • Preconditioned cells have increased proliferation • Preconditioning significantly increased mRNA levels of VEGF and bFGF •Preconditioned medium stimulated the formation of capillary-like structures |
| Chen et al. [20], 2017 China |
hADSC | In-vitro In-vivo | 1×105 cells/well 1×106 cells/well | DMOG at 50, 100 and 150 μmol/L and for 2, 4 and 7 days | •Preconditioned cells had a higher survival rate and lower death rate •50% decrease in mitochondrial mass with reduction of ROS •Increased angiogenic capabilities via increased HIF-1a -> VEGF, VEGF • Significantly promoted In-vivo survival of cells |
| Oses et al. [24], 2017 Chile |
hADSC | In-vitro | 7000 cells/cm2 | Cultured for 48 h in α-MEM without FBS with either 150 μM DFX, 400 μM DFX or double-distilled water (Control) | • Increased levels of HIF-1a •Upregulation of pro-angiogenic genes (VEGF-a, Angiopoietin) •Increased concentration of pro-angiogenic factors in the secretome of hADSC |
| Xue et al. [25], 2018 China |
hADSC-derived exosomes | In-vitro In-vivo | 2×106 cells 100 mg/mL of Exosomes | 1% O2 and 21% O2 | •Preconditioned exosomes significantly improved tube forming (in-vivo and In-vitro) •Angiogenesis inhibitory gene Vash1 was significantly decreased •HIF-1a and VEGF were increased considerably 6 days after hypoxia stimulation • Angiopoietin and Flk1 were considerably increased |
| Almeria et al. [21], 2019 Austria |
hADSC-derived extracellular vesicles | In-vitro | 3000 cells/cm2 | 21% or 5% O2 for 6 days | • Higher proliferation rate in preconditioned cells •Population doubling level and cell density were significantly higher in preconditioned cells #x2022;Total HUVECs length was significantly increased in preconditioned EV group |
| Han et al. [26], 2019 China |
hADSC-derived exosomes | In-vitro In-vivo | 5×103 cells/cm2 | Tri gas incubator with O2 at 5% with 5% CO2 and balanced nitrogen. | •Preconditioned Exosomes enhanced proliferation, migration, and tube-forming capacity of HUVECs •VEGF, EGF, bFGF, angiopoietin-1 were significantly upregulated •Preconditioned group improved neovascularization in-vivo fat grafting |
| Hwang et al. [22], 2020 Republic of Korea |
hADSC | In-vitro | 2.5×103 to 1×104 per well. | Multi-gas incubator at 37°C, 5% CO2, balanced nitrogen, and 1% O2 | •Cells cultured at 1% O2 showed significantly higher proliferation at 24 and 48 h • HIF-1a was increased by hypoxia •VEGF was expressed and secreted higher in preconditioned cells |
hADSC: Human adipose-derived stem cell; mRNA: Messenger ribonucleic acid; VEGF: Vascular endothelial growth factor; bFGF: Basic fibroblast growth factor; DMOG: Dimethyloxalylglycine; ROS: Reactive oxygen species; HIF-1a: Hypoxia-inducible factor -1alpha; A-mem: Alpha-minimum essential medium; FBS: Fetal bovine serum; DFX: Deferoxamine; HUVEC: Human umbilical vein endothelial cells; EV: Extracellular vesicles; EGF: Epidermal growth factor