Innovative therapeutic strategies for intrauterine adhesions: Role of umbilical cord mesenchymal stem cells in rat models.

Abstract

Intrauterine adhesions (IUAs) represent a considerable impediment to female reproductive health. Despite ongoing debate regarding the optimally efficacious route of administration and dosage of stem cells for IUA treatment, human umbilical cord-derived mesenchymal stem cells (UCMSCs) have emerged as a promising avenue for regenerative therapy. The present study aimed to investigate the potential effects of UCMSCs on IUAs and to further explore the most effective treatment route and dosages. In the present study, the therapeutic potential of UCMSCs in a constructed rat model of IUAs was evaluated. The efficacy of UCMSC administration through three different routes, namely intraperitoneal injection, in-site injection and caudal vein injection, was compared at three different doses of cells (0.5x10⁶, 1x10⁶ and 5x10⁶). The assessment parameters included endometrial thickness, glandular density and extent of fibrotic tissue, which were measured using HE staining and Masson staining and numbers of offspring. The IUA model group compared with the control group endometrial thickness decreased, glandular density decreased and the extent of fibrotic tissue increased, suggesting the IUA rat model had been successfully established. At 4 weeks post-treatment, an intraperitoneal injection of 1x10⁶ UCMSCs (the middle dose) was found to have led to a significant increase in endometrial thickness and glandular count, approaching the levels that were observed in the normal group. This dosage also notably reduced the level of fibrosis compared with that in both the higher and the lower doses, although this remained slightly higher compared with that observed in the normal group. Furthermore, the reproductive capability of the rats in the higher and middle dosage IUA rat model exhibited partial recovery post-treatment. In conclusion, the results of the present study suggest that the intraperitoneal administration of 1x10⁶ UCMSCs can provide a viable strategy for promoting endometrial regeneration and reducing fibrosis in IUA. In addition, this highlights the potential of UCMSC therapy as a means of clinical intervention for severe IUA, ultimately improving fertility outcomes, especially with regard to the specific dosage and intraperitoneal injection method.