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

Abstract

Objective: This study aimed to investigate the role of acellular amniotic membrane (AAM) loaded with adipose-derived mesenchymal stem cells (ADSCs) for the treatment of intrauterine adhesion. Methods: One hundred twenty female Spargue-Dawley rats were randomly divided into four groups: sham operation group (the uterus was picked out and incised without treatment), intrauterine adhesion group, the 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 PCR were used to explore the potential mechanism by which ADSCs modulated immune response and promoted endometrial regeneration. Results: On 14 days after surgery, the endometrial thickness, number of glands, and degree of fibrosis reduction in the ADSCs/AAM group was higher than those in the AAM group, and similar to the sham operation group. RNA sequencing analysis showed that ADSCs can modulate local immune responses and promote the formation of functional endometrium. Meanwhile, we found that ADSCs significantly decreased the levels of pro-inflammatory cytokines (TNF-α and IL-1β) and increased the levels of anti-inflammatory cytokines (bFGF and IL-6). Conclusion: Our results demonstrated that AAM loaded with ADSCs can result in the regeneration of injured endometrium and fibrosis reduction. Meanwhile, ADSCs also regulated the immune microenvironment, which was beneficial to functional endometrial recovery.