Exploring the Potential of Wharton's Jelly-Derived Mesenchymal Stem Cells as a Therapeutic Approach for Preterm Premature Rupture of Membranes

Preterm premature rupture of membranes (PPROM) is a major cause of preterm birth and neonatal morbidity, with no established treatment to restore membrane integrity. Mesenchymal stem cells (MSCs), known for their regenerative and immunomodulatory properties, harbor promising therapeutic potential for fetal membranes repair. This study aimed to evaluate the rapid barrier reinforcement effect of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) using <i>in vitro</i> and <i>ex vivo</i> models of PPROM. A wound healing assay was conducted to assess the effect of WJ-MSCs on human amniotic epithelial cells proliferation and migration. An <i>ex vivo</i> PPROM model was established using incised human fetal membranes to simulate membrane rupture. WJ-MSCs were directly applied to the lesion site at varying doses. Therapeutic efficacy was evaluated by a leak test and histological analysis. WJ-MSCs and their conditioned medium significantly enhanced epithelial wound closure <i>in vitro</i>, demonstrating that soluble paracrine factors secreted by WJ-MSCs have the potential to aid membrane injury restoration. In the <i>ex vivo</i> PPROM model, WJ-MSCs treatment reduced both leakage area and frequency of fetal membranes, with the most significant effect observed at a medium dose (5.0×10⁵ cells). Histological evaluations revealed partial recovery of the fetal membranes, particularly the chorion layer. These findings suggest that WJ-MSCs contribute to rapid barrier reinforcement of injured fetal membranes. Taken together, WJ-MSCs enhance epithelial healing and support restoration of membrane integrity, highlighting their potential as a therapeutic approach for PPROM. Further, <i>in vivo</i> studies are required to confirm therapeutic efficacy and evaluate safety.