Lessons from human umbilical cord: gender differences in stem cells from Wharton's jelly

Objective: To study the molecular features of mesenchymal stem cells from Wharton Jelly (WJ-MSCs) of umbilical cord to predict their differentiation capacity. Design: Comparison of gene expression from mesenchymal stem cells of male and female umbilical cord Setting: University hospital Patient (s): umbilical cords (n = 12, 6 males and 6 females) retrieved from spontaneous full-term vaginal delivery of healthy women Intervention: we analyzed the expression of the stemness related genes C-MYC, OCT4, SOX2 and NANOG and of the epigenetic modulating gene DNA-methyltransferase 1 (DNMT1). Mean outcome measure: WJ-MSCs were isolated by standard procedures and immunophenotypically characterized. Gene expression analysis of stemness related genes and the epigenetic modulating gene DNMT1 were performed by real-time PCR Results: expression of the OCT4 and DNMT1 genes was significantly higher in WJ- MSCs isolated from male subjects, as compared to MSCs isolated from female-derived WJ. The resulting higher expression of OCT4 and DNMT1 in WJ-MSCs from males as compared with female WJ-MSCs for the first time identifies a specific relationship between stemness genes, an epigenetic modulator, and gender differences. Conclusion: our findings disclose novel biomedical implications in WJ-MSCs related to the sex of the donor, thus providing additional cues to exploit their regenerative potential in allogenic transplantation.