Mesenchymal stem cell exosomes and platelet-rich fibrin repair endometrial injury in rats: Insights into histological regeneration, inflammation modulation, and molecular signaling crosstalk.

Abstract

INTRODUCTION: Endometrial injury is a leading cause of impaired endometrial receptivity, fibrosis, and defective vascularization, resulting in implantation failure and infertility. Conventional treatments such as cell transplantation often provide only partial and inconsistent recovery. Injectable platelet-rich fibrin (i-PRF) offers a three-dimensional fibrin network with sustained release of growth factors, creating a microenvironment that supports angiogenesis, epithelial and stromal proliferation, and cell migration. Mesenchymal stem cell-derived exosomes (MSCs-Exo) are enriched with microRNAs, growth factors, and proteins that modulate gene expression, inhibit apoptosis, suppress inflammation, and activate angiogenic signaling (Abd-Rabou et al., 2023; Aglan et al., 2024). Although each therapy has demonstrated regenerative potential, their combined effect in endometrial repair remains unexplored. AIM: This study aimed to evaluate the therapeutic efficacy of i-PRF, MSCs-Exo, and their combination in a rat model of ethanol-induced endometrial injury. METHODS: Adult female rats were randomly assigned to five groups: Group 1 (Sham), Group 2 (ethanol-injured model), Group 3 (i-PRF), Group 4 (MSCs-Exo), and Group 5 (i-PRF + MSCs-Exo). RESULTS: After three estrous cycles, uterine tissues were collected for assessment of endometrial repair. Intrauterine co-administration of i-PRF and MSCs-Exo significantly down-regulated profibrotic markers (α-SMA, TGF-β1), inflammatory mediators (TNF-α, IL-1β, MMP-9), and oxidative stress/DNA damage indices, while markedly up-regulating regenerative and angiogenic markers (Ki-67, cytokeratin-18, vimentin, VEGF) and restoring endometrial thickness, glandular density, and vascular architecture. DISCUSSION AND CONCLUSION: The combination therapy surpassed the effects of either treatment alone, amplifying regenerative signaling and accelerating endometrial repair, and thus represents a potent, cell-free therapeutic strategy for endometrial injury with strong translational potential for clinical application.