Effect of CXCL12/CXCR4 on migration of decidua-derived mesenchymal stem cells from pregnancies with preeclampsia

Problem: Systemic immuno-inflammatory response caused by maternal immune imbalance is central to the pathogenesis of preeclampsia (PE). We hypothesized that changes in the number of decidual mesenchymal stem cells (dMSCs) may be associated with maternal immune imbalance. We aimed to evaluate the expression of CXCL12/CXCR4 axis in patients with PE and its influence on the migration behavior of dMSCs, to further clarify the pathogenesis of PE. Method of study: Fourteen women with PE and 11 controls were included. DMSCs were extracted from decidual tissue by type II collagenase digestion and adherence. ELISA and immunohistochemistry analysis were used to measure serum and tissue levels of CXCL12. Q-PCR and Western blotting were used to detect CXCR4 expression on dMSCs, whereas transwell assay was used to measure the migration ability of dMSCs. Results: Decidual mesenchymal stem cells from women with PE showed higher expressions of CXCR4 and HIF-1 alpha than the dMSCs of controls did. Tissues from women with PE showed the highest CXCL12 levels in the decidua, followed by the placenta and umbilical cord, whereas tissues from controls showed the highest CXCL2 levels in the umbilical cord, followed by the placenta and decidua. dMSCs from women with PE showed possibly higher migration ability than that of dMSCs from controls, under the induction of CXCL12, whereas dMSCs showed a decreasing trend in hypoxic than in normoxic environment. Conclusion: Decidual mesenchymal stem cells from women with PE can migrate to the decidua layer with the concentration gradient of CXCL12, which may play a role in the occurrence and development of PE.