Insight in Hypoxia-Mimetic Agents as Potential Tools for Mesenchymal Stem Cell Priming in Regenerative Medicine

Table 3

Effect of pharmaceutically and chemically derived hypoxia on MSC viability, proliferation, and clonogenicity.

Treatment conditions		Stem cell type	The effect compared to normoxia (methods of analysis)	Ref.
An agent/concentration	Time
DFO/0.1 μM	53 d	hBM-MSC	Proliferation increased (Incucyte HD Imaging system)	[61]
DFO/10 μM	2 d	hBM-MSC	The genes related to glycolysis (HK2, PDK-1, BNIP3, LDHA), viability, and survival upregulated (microarray analysis)	[61]
DFO/10 μM	53 d	hBM-MSC	Proliferation inhibited at concentrations of 10 μM and higher (Incucyte HD Imaging system)	[61]
DFO/50 μM	12 h	hBM-MSC	Proliferation as effective as for 2 d in 3 μM DFO (Incucyte HD Imaging system), HIF-1α upregulated (microarray analysis)	[99]
DFO/50 μM	1-3 d	rBM-MSC	Viability increased (MTT)	[100]
DFO/50-500 μM	1 d	hAD-MSC	Viability unchanged (CellTiter 96 Aqueous kit)	[102]
DFO/100 μM	12 h	rBM-MSC	HIF-1α increased (qRT-PCR)	[100]
DFO/100 μM	1 d	rBM-MSC	HIF-1α increased (WB)	[100]
DFO/100 μM	1-3 d	rBM-MSC	Viability increased (MTT)	[100]
DFO/100 μM	2 d	hWJ-MSC	HIF-1α increased (WB)	[115]
DFO/120 μM	2 d	hUC-MSC	Cell viability was DPO concentration-dependent, cell viability decreased above 120 μM DFO (MTT)	[97]
CoCl2/50-300 μM	1 d	hAD-MSC	Viability increased (MTT)	[102]
CoCl2/100 μM	1-2 d	hDP-MSC; hUC-MSC; hAD-MSC	Viability increased (MTT)	[53]
CoCl2/100 μM	2 d	hDP-MSC; hUC-MSC; hAD-MSC	HIF-1α increased in DP- and UC-MSC and maintained in AD-MSC (WB)	[53]
CoCl2/100 μM	2 d	hUC-MSC	Viability decreased above 100 μM CoCl2 (MTT)	[97]
CoCl2/100 μM	6 d	Coculture; hBM-MSC; HUVEC	The higher proliferation of hBM-MSC in coculture (crystal violet staining), reduced viability of hBM-MSC	[52]
CoCl2/0.5 mM	1 d	hAD-MSC	Reduced viability (MTT)	[102]
DMOG/100 μM+SD	1 d	rBM-MSC	Proliferation maintained (Trypan Blue staining, cell count), PI3K/Akt signaling activated (WB), HIF-1α increased (WB)	[103]
DMOG/0.5 mM + SD	1 d	rBM-MSC	Proliferation maintained (Trypan Blue staining, cell count), PI3K/Akt signaling activated (WB), HIF-1α increased (WB)	[103]
DMOG/0.5 mM+ 1%O2	2 d	rBM-MSC	HIF-1α increased (WB)	[80]
DMOG/0.5 mM	6 d	Coculture; hBM-MSC; HUVEC	The higher proliferation of hBM-MSC in coculture (crystal violet staining), increased viability of hBM-MSC	[52]
DMOG/1 mM	1 d	rBM-MSC	Viability increased in vitro (Hoechst 33342 staining), HIF-1α increased (WB), glucose transporter 1 increased (WB), the pAKT level increased (WB), increase survival of MSC after transplantation into ischemic heart (a rat model) (TUNEL assay), time-dependent protective effect against cell death in vitro (Trypan Blue staining, cell count)	[92]
DMOG/1 mM + SD	1 d	rBM-MSC	Proliferation maintained (Trypan Blue staining, cell count), PI3K/Akt signaling activated (WB), HIF-1α increased (WB)	[103]
DMOG/5 mM + SD	1 d	rBM-MSC	Proliferation decreased (Trypan Blue staining, cell count)	[103]
ISO/2%	4 h	hBM-MSC	Cell metabolic activity increased after 4 h, significantly reduced after 6 h at ISO concentrations above 2% (MTT), HIF-1α increased (WB), the PI3K/Akt signaling activated (WB), the percentage of apoptotic cells significantly reduced after treatment with 1-2% ISO for 6 h (flow cytometry)	[98]
DNP/0.25 mM	20 min	Coculture; rBM-MSC; CM	The viability significantly increased (PKH26, flow cytometry)	[94]

20 minutes of treatment with 0.25 mM and then reoxidation either 2 or 24 hours in 21% O₂; d: day/days; h: human; m: mouse; r: rat; SD: serum deprivation; CM: cardiomyocytes; HUVEC: human umbilical vein endothelial cells.