Investigating the abnormalities and potential therapeutic targets in umbilical cord mesenchymal stem cells from preeclampsia.

BACKGROUND

Damaged cells are influenced by their microenvironment, which may lead to abnormalities. In preeclampsia (PE), several abnormal changes can occur that affect the umbilical cord and, consequently, umbilical cord mesenchymal stem cells (UCMSCs). Understanding these mechanisms can optimize therapeutic strategies for UCMSCs, thereby in addressing a range of complex disease microenvironments.

METHODS

Flow cytometry analysis, alizarin red staining and oil red O staining were utilized to detect the characteristic surface markers and assess the differentiation potential of UCMSCs. The CCK8 and EdU assays were used to assess cell proliferation. RNA sequencing was performed on UCMSCs from both donor groups. A senolytic combination therapy was applied to target senescent cells, with JC-1 fluorescence staining assay, SA-β-gal staining and gene expression to identify cellular senescence. Immunofluorescence analysis was conducted to examine proliferation and cytoskeletal changes.

RESULTS

UCMSCs from both donor groups did exhibit significant differences in surface markers and differentiation capacity. UCMSCs-PE demonstrated reduced cell proliferation. Transcriptome analysis revealed notable alterations, particularly in senescence and cytoskeletal changes, which were validated by increased SA-β-gal activity, impaired mitochondrial function, and cytoskeletal staining. The senescence phenotype and cytoskeletal integrity in the UCMSCs-PE group were notably improved by the combination of dasatinib and quercetin.

CONCLUSIONS

Our study suggests that senescence and cytoskeletal abnormalities may represent notable changes in UCMSCs-PE. Cellular senescence may play a critical role in the physiology of PE, highlighting the potential of targeting senescence mechanisms as a novel approach.