Transplantation of acellularized amniotic membrane seeded with adipose-derived mesenchymal stem cells in a rat model of intrauterine adhesion

Abstract: Background Intrauterine adhesion (IUA) is characterized by the formation of fibrosis that prevent the regeneration of functional endometrium. Although various clinical approaches have been used to reconstruct the anatomy and promote the restoration of functional endometrium, the high risk of recurrence after surgery remains a major challenge. Application of tissue engineering offers new therapeutic strategies. Aim The aim of this study was to investigate the role of acellularized amniotic membrane (AAM) loaded with adipose-derived mesenchymal stem cells (ADSCs) in reducing IUA, and promoting the regeneration of damaged endometrium. Methods 96 female Spargue-Dawley (SD) rats were randomly divided into four groups: sham operation group, IUA model group, experimental group treated with AAM, and experimental group treated with AAM loaded with ADSCs. Histological and immunohistochemical analysis were performed on 3, 7, and 14 days after surgery to evaluate the degree of uterine fibrosis and regeneration of injured endometrium. RNA sequencing and real-time polymerase chain reaction (RT-PCR) were used to explore the potential mechanism by which ADSCs modulated immune response and promoted endometrial regeneration. Results At 14 days after surgery, the endometrial thickening, the number of glands and the degree of reduced fibrosis in the ADSCs/AAM was higher than those in AAM group, and similar to sham group. RNA sequencing analysis showed that ADSCs can modulate local immune responses, and promote the formation of functional endometrium. Meanwhile, we found that transplantation of ADSCs significantly decreased the expression of pro-inflammatory cytokines expression (TNF-α and IL-1β), and increased the expression of anti-inflammatory cytokines (bFGF, and IL-6). Conclusion Our results demonstrated that AAM loaded with ADSCs can promote the regeneration of injured endometrium and reduce fibrosis formation. Meanwhile, ADSCs also regulated the immune microenvironment, which is beneficial to functional endometrial regeneration.