Abstract
BackgroundCesarean scar defect (CSD) is characterized by the presence of fibrotic tissue and decreased muscular density which is induced by cesarean section. Serious CSD may eventually result in infertility or obstetrical complications. Human amniotic epithelial cells (hAECs) have shown great promise in tissue regeneration. This study aims to investigate whether hAEC transplantation has the therapeutic effects on the rat uterine scar following full-thickness injury.MethodsA rat uterine scar model was established by excising the full-thickness uterine wall of about 1.0 cm in length and 1/2–2/3 of the total circumference in width. At day 30 post-surgery, hAECs were transplanted into the uterine scar. At day 30 and 60 post-transplantation, hematoxylin and eosin (H&E) staining, Masson staining, and IHC staining for vWF, VEGFA, α-SMA, and MMP-8 were performed to evaluate the regeneration of the scarred uterus and the underlying mechanism. Pregnancy outcomes were assessed at day 60 after hAEC transplantation. Finally, hAECs were incubated with hydrogen peroxide to verify the paracrine effect of hAECs.ResultsCollagen deposition, thin myometrium, and injured endometrium were observed in the rat uterine scar model. After hAEC transplantation, collagen deposition in the uterine scar decreased, and myometrial and endometrial recovery was facilitated. hAEC transplantation also increased the fetus number implanted within the scarred area. Moreover, we found hAECs promoted angiogenesis via upregulation of VEGFA and decreased collagen deposition by upregulating MMP-8 in the uterine scar. The in vitro studies further demonstrated an increase in the expression level of MMP-8 in hAECs cultured with hydrogen peroxide.ConclusionsThese results suggested that hAEC transplantation may be efficacious in the functional repair and collagen degradation of uterine scars, which provides a new therapeutic strategy to CSD.
Highlights
Cesarean scar defect (CSD) is characterized by the presence of fibrotic tissue and decreased muscular density which is induced by cesarean section
According to hematoxylin and eosin (H&E) staining and Masson’s trichrome staining, we observed that wounded uteruses had few endometrial glands and thin endometrium in the surgical region compared to the normal rat uterus at day 30 after injury (Fig. 2D)
Enzyme-linked immunosorbent assay (ELISA) and western blot analysis Here we investigated the changes in the Matrix metalloproteinase-8 (MMP-8) levels in Human amniotic epithelial cells (hAECs) after exposure to H2O2 in vitro by ELISA and western blots
Summary
Cesarean scar defect (CSD) is characterized by the presence of fibrotic tissue and decreased muscular density which is induced by cesarean section. Serious CSD may eventually result in infertility or obstetrical complications. The long-term complication of CS, cesarean scar defect (CSD), has been of great concern. CSD, called isthmocele or niche, is defined as discontinuation of the myometrium in the uterine scar of the cesarean section due to defective healing [3, 4]. The pathological features of CSD are the presence of fibrotic tissue and significantly decreased muscular density in the myometrium covering the scar [5]. CSD could trigger infertility and obstetric complications in subsequent pregnancies like scar pregnancy, placenta accrete, placenta previa, and uterine rupture [9]. It is important to develop a novel therapy for CSD
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