Hypoxic Preconditioning Enhances Cellular Viability and Migratory Ability: Role of DANCR/miR-656-3p/HIF-1 & alpha; Axis in Placental Mesenchymal Stem Cells

Preeclampsia (PE) is a common complication of pregnancy characterized by new-onset hypertension, albuminuria, or end-stage organ dysfunction, which is seriously harmful to maternal and infant health. Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from extraembryonic mesoderm. They have the potential for self-renewal, multidirectional differentiation, immunomodulation, and tissue regeneration. Several in vivo and in vitro experiments have confirmed that MSCs can delay the pathological progression of PE and improve maternal and fetal outcomes. However, the major limitations in the application of MSCs are their low-survival rates in ischemic and hypoxic disease areas after transplantation and their low rate of successful migration to the diseased regions. Therefore, enhancing cell viability and migration ability of MSCs in both ischemic and anoxic environments is important. This study aimed to investigate the effects of hypoxic preconditioning on the viability and migration ability of placental mesenchymal stem cells (PMSCs) and their underlying mechanisms. In this study, we found that hypoxic preconditioning enhanced the viability and migration ability of PMSCs, increased the expression of DANCR and hypoxia-inducible factor-1 & alpha; (HIF-1 & alpha;), and decreased the expression of miR-656-3p in PMSCs. Inhibiting the expression of HIF-1 & alpha; and DACNR in PMSCs under hypoxia can inhibit the promotive effect of hypoxic preconditioning on viability and migration ability. In addition, RNA pull down and double luciferase assays confirmed that miR-656-3p could directly bind to DANCR and HIF-1 & alpha;. In conclusion, our study showed that hypoxia could promote the viability and migration ability of PMSCs through the DANCR/miR-656-3p/HIF-1 & alpha; axis.