Background: A previous caesarean scar defect (PCSD), also referred to as a caesarean scar diverticulum, is a highly prevalent condition, resulting in infertility and uterine rupture. Currently, there are no effective treatment options for treating this condition. Evidence indicates that mesenchymal stem cells (MSCs) promote tissue repair and regeneration. Furthermore, studies have demonstrated that the therapeutic effects of MSCs are mediated by exosomes produced through a paracrine mechanism. Therefore, this study aims to explore the potential of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) in repairing post-caesarean uterine scar defects in rat models.

Methods: A rat model of PCSD was established using the combination of mechanical injury and infection. Two weeks post-surgery, hUCMSC-Exos were transplanted into the uterine scar area. At 8 weeks post-transplantation, endometrial thickness, myometrial thickness, and fibrosis were assessed using H&E and Masson's trichrome staining. Immunohistochemistry (IHC) and Western blot analysis were performed to evaluate α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and vascular endothelial growth factor (VEGF) protein levels. The remaining female rats were mated with males, and fertility was examined by euthanizing them at 19 days post-conception.

Results: Excessive collagen deposition and thinning of the endometrium and myometrium were observed in PCSD model rats. Following hUCMSC-Exos transplantation, collagen deposition in the uterine scar decreased (p < 0.001), while endometrium thickness, myometrium thickness, and angiogenesis levels all significantly increased (p < 0.001). Furthermore, TGF-β1 levels decreased (p < 0.01), while α-SMA and VEGF levels increased (p < 0.001) after hUCMSC-Exos treatment. Additionally, pregnancy rates improved, and the number of implanted fetuses within the scar area increased (p < 0.01).

Conclusion: hUCMSC-Exos exerts significant therapeutic effects by improving both the morphology and function in a previous caesarean scar defect model. hUCMSC-Exos offers a novel, cell-free therapeutic option for patients with PCSD.