Review Article

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

Table 5

Effect of pharmaceutically and chemically derived hypoxia pretreatment on MSC differentiation.

Treatment conditionsStem cell typeThe effect compared to normoxia (methods of analysis)Ref
An agent/concentrationTime

DFO/3 μMTreatment for 14 dhBM-MSCOsteogenic (Alizarin Red staining, 14 d) and adipogenic (Oil Red staining, 14 d) potential decreased[61]
DFO/15 μMTreatment for 7 dhBM-MSCALP increased (WB, 7 d)[120]
DFO/15 μMTreatment for 21 dhBM-MSCOsteogenic potential increased (Alizarin Red staining, 21 d), ALP, RUNX2, and OC upregulated (qRT-PCR), osteogenesis through β-catenin signaling increased (WB)[120]
DFO/50 μMTreatment for 21 dhBM-MSCChondrogenesis (Alcian Blue, 21 d) and SOX9 expression (RT-PCR, 7 d) slightly increased[124]
DFO/120 μMTreatment for 8 dmBM-MSCAdipogenic potential preserved (Sudan Black staining, 8 d), Oct4 expression maintained (qRT-PCR)[123]
DFO/120 μMTreatment for 21 dhUC-MSCOsteogenic (Von Kossa staining, 21 d), and adipogenic (Oil Red staining, 21 d) potential preserved[97]
CoCl2/100 μMPretreatment for 1-2 dmC3H/10T1/2-MSCOsteogenesis (Alizarin Red staining, 18 d) and expression of the Col I, Bglap, and Alp genes (RT-PCR, 10 d) enhanced, adipogenesis (Oil Red staining, 5 d) and expression of the Ap2, C/ebpα, and Pparγ genes (RT-PCR, 5 d) reduced, chondrogenesis (Alcian Blue staining, 14 d) and expression of SOX9, Col II, and ACAN genes (RT-PCR, 10 d) enhanced[101]
CoCl2/100 μMPretreatment for 2 dhDP-MSC
hUC-MSC
hAD-MSC
Chondrogenesis (Alcian Blue, 28 d) in AD- and UC-MSC increased, in DP-MSC—not detected, cell-source dependent changes of the expression of the following genes: COL2A1, ACAN, SOX9, and VCAN (RT-PCR): DP-MSC–SOX9 (after 7 d up, and after 14, 21, and 28 d downregulated), VCAN (after 7, 14, 21, and 28 d upregulated), COL2A1 and ACAN not detected
UC-MSC–SOX9 (after 7, 28 d down, and after 14 and 21 d upregulated), COL2A1, ACAN, and VCAN (after 7,14, 21, and 28 d—upregulated)
AD-MSC–SOX9 (after 7 d up-, and after 14, 21, and 28 d downregulated), COL2A1 (after 7,14, 21, and 28 d upregulated), and ACAN upregulated only after 14 d, VCAN (after 7,14, 21, and 28 d downregulated)
[53]
CoCl2/100 μMTreatment for 8 dmBM-MSCAdipogenic potential preserved (Sudan Black staining, 8 d), Oct4 expression maintained (qRT-PCR)[123]
CoCl2/100 μMTreatment for 9 dCoculture
hBM-MSC
HUVEC
Osteogenic potential retained (Alizarin Red, nine days), expression of RUNX2, ALP, and COLIA1 maintained (qRT-PCR)[52]
CoCl2/100 μMTreatment for 21 dhUC-MSCOsteogenic (Von Kossa staining, 21 d), and adipogenic (Oil Red staining, 21 d) potential preserved[97]
CoCl2/100 μMTreatment for 21 dhBM-MSCChondrogenesis (Alcian Blue, 21 d) and SOX9 expression (RT-PCR 7d) maintained[124]
DMOG/200 μMTreatment for 21 dhBM-MSCChondrogenesis (Alcian Blue, 21 d) and SOX9 and RUNX2 expression (RT-PCR, 7 d) increased[124]
DMOG/500 μMPretreatment for 2 drBM-MSCOsteogenesis (Alizarin Red S, 21 d) and ALP activity (7 d) increased[80]
DMOG/500 μM +1%O2Pretreatment for 2 drBM-MSCOsteogenesis (Alizarin Red S, 21 d) and ALP activity (7 d) increased[80]
DMOG/500 μMTreatment for 9 dCoculture
hBM-MSC
HUVEC
Osteogenic potential retained (Alizarin Red, 9 d), expression of RUNX2 maintained (qRT-PCR), expression of ALP and COLIA1 increased (qRT-PCR)[52]

d: day/days; h: human; m: mouse; r: rat.