Abstract
BackgroundMesenchymal stem cells (MSCs) have diverse functions in regulating injury and inflammation through the secretion of extracellular vesicles (EVs).MethodsIn this study, we investigated the systemic administration of extracellular vesicles derived from human umbilical cord mesenchymal stem cells (UCMSCs-EVs) as a therapeutic agent for intrauterine adhesions (IUAs) caused by endometrial injury. Additionally, we investigated the therapeutic impact of both UCMSCs-EVs and estrogen either separately or in combination in a rat model. The inflammation, vascularization, proliferation, and extent of fibrosis were assessed by a histopathological and immunohistochemical assessment using transforming growth factor (TGF)-β as a fibrotic marker and vascular endothelial growth factor (VEGF) as a vascular marker. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6 (inflammatory cytokines), CD140b (a marker of endometrial stem cells), and RUNX2 (an antifibrotic factor). Finally, Western blotting was used to evaluate collagen I and β-actin expression.ResultsThe therapeutic groups treated with either UCMSCs-EVs alone or combined with estrogen exhibited a significant decrease in inflammation and fibrosis (TNF-α, TGF-β, IL-1, IL-6, RUNX2, and collagen-I) as well as a significant decrease in vascularization (VEGF) compared with the untreated rats with IUAs. The most significant results were obtained in animals with IUAs that received a combined therapy of UCMSCs-EVs and estrogen.ConclusionsWe conclude that the synergistic action of human UCMSCs-EVs combined with estrogen provides a highly effective alternative regenerative agent in IUA treatment.
Highlights
Mesenchymal stem cells (MSCs) have diverse functions in regulating injury and inflammation through the secretion of extracellular vesicles (EVs)
Histological results hematoxylin and eosin (H&E) results An examination of the H&E-stained uterine sections revealed that the endometrium contained surface columnar epithelium cells overlying a thick layer of lamina propria with compact stromal cells, numerous tiny blood vessels (BV), and endometrial glands (EG)
Immunohistochemistry results To assess the extent of intrauterine adhesions (IUAs), we evaluated transforming growth factor (TGF)-β immunoexpression since TGF-β plays an important role in fibrosis formation
Summary
Mesenchymal stem cells (MSCs) have diverse functions in regulating injury and inflammation through the secretion of extracellular vesicles (EVs). Intrauterine adhesion (IUA), which is caused by damage to the endometrial basement membrane and exposure of myometrial tissue, is a common gynecological disease that is referred to as Asherman’s syndrome and is characterized by spanomenorrhea, amenorrhea, infertility, recurrent miscarriage, abdominal pain, and other complications later in pregnancy [1]. Infection or trauma are the most common causes of such IUAs, especially after pregnancy. Because the pathogenesis of IUAs has not been fully elucidated, the successful pregnancy rate remains low despite advances in therapeutic modalities [2]. Treatment of IUAs aims to rebuild a normal uterine cavity and restore uterine function. Severe and dense IUAs represent a real therapeutic challenge and have a poor prognosis. Treatment is difficult and has a poor prognosis [2]
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