Umbilical Cord Mesenchymal Stem Cells Improve PINK1/PARKIN-Mediated Mitophagy Inhibition in Preeclampsia

Preeclampsia (PE) is a progressive multisystem disorder that arises after 20 weeks of gestation and poses severe risks to both maternal and fetal health. Umbilical cord mesenchymal stem cells (UC-MSCs) exhibit antioxidant and pro-angiogenic properties, which have been shown to be effective in treating various diseases.

HTR8/SVneo cells were induced by lipopolysaccharide (LPS) to establish a PE cell model. Western blot (WB) and real-time quantitative PCR (RT-qPCR) were conducted to detect the expression of genes related to mitophagy. Meanwhile, ATP level was detected using an ATP content assay kit and mitochondrial membrane potential (MMP) level was detected under a fluorescence microscope using an MMP detection kit. Next, a PE rat model was induced using N(ω)-nitro-l-arginine methyl ester (L-NAME), followed by UC-MSCs transplantation. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of PE biomarkers, and the expression of mitophagy related genes was assessed via RT-qPCR, WB, and immunohistochemistry.

UC-MSCs modulated the levels of Phosphatase and Tensin Homolog-induced Kinase 1 (PINK1), Parkin RBR E3 ubiquitin protein ligase (PARKIN), reversed the inhibition of mitophagy in the PE model and increased both ATP content and MMP. Importantly, UC-MSCs alleviated hypertension and proteinuria in PE rats, improved pregnancy outcomes, and mitigated the imbalance in angiogenesis.

This study demonstrates that UC-MSCs improve PE trophoblast injury and vascularization imbalance through regulating mitochondrial autophagy. Our results indicate that UC-MSCs may hold significant potential for treating PE.Clinical trial number Not applicable.