Transplantation of human umbilical cord mesenchymal stem cells induces angiogenesis and promotes repair of uterine scars in rats

Abstract: Background Uterine scar after cesarean section (CS) is an important cause of intrauterine adhesion, amenorrhea, uterine rupture, and infertility in females. Disruptions of angiogenesis play a critical role in the healing of uterine scars. In this study, we investigated the effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) on angiogenesis regeneration in uterine scars in rats following full-thickness excision of uterine walls. Methods Approximately 2.0 cm was excised along the uterine wall in each uterine horn to establish a rat model of uterine scars. Hematoxylin and eosin (H&E) staining was applied to observe the tissue structure. Masson trichrome staining was used to reveal collagen deposition. Angiogenesis factors (FGF-2, VEGFA, and PDGFB) were detected via western blotting. The fate of transplanted hUC-MSCs was assessed using in vivo fluorescence imaging. The differential expression of microRNA and function prediction was detected using high-throughput sequencing. Results hUC-MSCs significantly improved the morphology of the tissue structure and alleviated fibrosis in general on days 15, 30, and 60 of transplantation in the hUC-MSC groups. Moreover, the expressions of all three angiogenesis factors were increased at days 15 and 30 post-transplantation. In GFP analyses, although hUC-MSCs were observed on the uterine wall at days 15 and 30, those signals gradually weakened and then accumulated in other organs at day 60. In addition, abundant hUC-MSC-specific microRNAs targeted the cell pathways of angiogenesis and the PI3K/AKT signaling pathway. Conclusion hUC-MSC transplantation contributed to the repair of uterine scars, mainly through the suppression of excessive fibrosis and the enhancement of vascular remodeling.