The effect and mechanism of human amniotic mesenchymal stem cells on scar formation in rat uterine incision

Abstract

Cesarean section (CS) scar tissue fibrosis and decreased muscle density increase the risk of uterine rupture and placental implantation in subsequent pregnancies. Given the potent anti-fibrotic and regenerative properties of human amniotic mesenchymal stem cells (hAMSCs), this study investigated their therapeutic potential in repairing uterine scars in a rat model. A full-thickness uterine wall excision model was established to mimic CS scarring. hAMSCs were transplanted at the edge of the incision. Myometrial thickness and collagen deposition within the scar were assessed histologically using hematoxylin and eosin (H&E) and Masson’s staining. Immunohistochemistry evaluated the expression of MMP8, TGF-β1, VEGFA, and α-SMA within the scar region. mRNA transcriptome sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to explore possible mechanisms. A total of 110 rats were used in the study, 30 in the sham group, 40 in the phosphate-buffered saline (PBS) control group and 40 in the hAMSCs treatment group. Compared with the PBS group, the hAMSCs group exhibited a 35% reduction in collagen fiber area and a 28% increase in smooth muscle cell density (P < 0.05). The MMP8, VEGFA, and α-SAM expressions in the uterine scar area of rats increased, whereas the TGF-β1 expression decreased (P < 0.05). Transcriptome sequencing and real-time fluorescence quantitative PCR results showed that the expression levels of Wnt4, Fzd5, Wnt5a, and PPARD genes were lower in the uterine scar region of rats in the hAMSCs group compared with those in the PBS group. Transplantation of hAMSCs inhibits scar formation in uterine wounds and promotes regeneration of smooth muscle tissue and neovascularization, which in turn promotes uterine wound repair. This effect may be related to the activation of Wnt pathway and the inhibition of PPARD gene expression.