OBJECTIVE: Mesenchymal Stromal Cells have been highlighted as an effective antioxidant therapy. Indeed, anomalies in PDMSCs antioxidant defences might cause/contribute to the increased oxidative stress (OxS) typical of PE placentae. Herein, we compared the release of antioxidant proteins and investigated the expression of the anti-oxidant enzymes Catalase (CAT) and Superoxide Dismutase1 (SOD1) and of OxS-triggered cell death modulators PARP1, Caspase3 and LDOC1 in normal and PE-PDMSCs. Finally, we tested the hypothesis that PDMSCs-CM (Conditioned-Media) could restore CAT and SOD1 in H2O2-treated villous explants.
METHODS: PDMSCs were isolated from control (n=10) and PE (n=10) placentae. At passage 5, cells were plated (1x105 cells/ml) in DMEM without FBS. After 48h, CM were collected and total antioxidant capacity was tested by Cayman’s Antioxidant Assay. Control (n=24) villous explants were treated for 24h by H2O2 and next by control PDMSCs-CM for 48h. CAT, SOD1, PARP1, Caspase3 and LDOC1 gene expression were evaluated by Real Time PCR.
RESULTS: We reported a lower total antioxidant capacity (1.42 Fold Decrease) in PE-PDMSCs relative to control. We reported decreased CAT and SOD1 and increased PARP1 (p=0.03), Caspase3 (p=0.04) and LDOC1 (p=0.05) gene levels in PE- relative to control PDMSCs. After 24h with H2O2, normal PDMSCs-CM treatment increased CAT and SOD1 and significantly decreased of PARP1 (p=0.02), Caspase3 and LDOC1 mRNA levels relative to controls.
CONCLUSIONS: Herein, we demonstrated that that pathological PE-PDMSCs are characterized by aberrant antioxidant properties followed by increased production of OxS-related cell death effectors. Moreover, PDMSCs-CM promotes the expression of anti-oxidant enzymes thus inhibiting OxS-mediated cell death. Indeed, our data suggest that PDMSCs-CM could be used to neutralize the exacerbated OxS typical of PE placentae thus opening to novel PDMSCs-based therapeutic options.