Abstract
Background Abnormal endometrial repair after injury results in the formation of intrauterine adhesions (IUA) and a thin endometrium, which are key causes for implantation failure and infertility. Stem cell transplantation offers a potential alternative for some cases of severe Asherman's syndrome that cannot be treated with surgery or hormonal therapy. Umbilical cord-derived mesenchymal stem cells (UCMSCs) have been reported to repair the damaged endometrium. However, there is no report on the effects of UCMSCs previously seeded on human acellular amniotic matrix (AAM) on endometrial injury. Methods Absolute ethanol was injected into rat uteri to damage the endometrium. UCMSCs previously seeded on AAM were surgically transplanted. Using a variety of methods, the treatment response was assessed by endometrial thickness, endometrial biomarker expression, endometrial receptivity, cell proliferation, and inflammatory factors. Results Endometrial thickness was markedly improved after UCMSC-AAM transplantation. The expression of endometrial biomarkers, namely, vimentin, cytokeratin, and integrin β3, in treated rats increased compared with untreated rats. In the UCMSC-AAM group, the VEGF expression decreased, whereas that of MMP9 increased compared with the injury group. Moreover, in the AAM group, the MMP9 expression increased. The expression of proinflammatory factors (IL-2, TNFα, and IFN-γ) in the UCMSC-AAM group decreased compared with the untreated group, whereas the expression of anti-inflammatory factors (IL-4, IL-10) increased significantly. Conclusions UCMSC transplantation using AAM as the carrier can be applied to treat endometrial injury in rats. The successful preparation of lyophilized AAM provides the possibility of secondary infectious disease screening and amniotic matrix quality detection, followed by retrospective analysis. The UCMSC-AAM complex may promote the better application of UCMSCs on the treatment of injured endometrium.
Highlights
Endometrial injury, which affects endometrial thickness and involves intrauterine adhesions (IUA) formation, is a cause of amenorrhea, implantation failure, and infertility [1], which have been on the rise due to the continuous increase in the rates of abortions and hysterectomies in China [2, 3]
There were no cells on the surfaces of both FAAM and FDAAM
The FAAM mesh was relatively loose compared to that of FDAAM preserved at low temperature for half a year after lyophilization
Summary
Endometrial injury, which affects endometrial thickness and involves IUA formation, is a cause of amenorrhea, implantation failure, and infertility [1], which have been on the rise due to the continuous increase in the rates of abortions and hysterectomies in China [2, 3]. To increase the thickness of the endometrium, sildenafil and granulocyte colony stimulating factor (G-CSF) are applied [5] These entities have very limited effects on the restoration of endometrial function, especially in cases of severe basal layer damage [6, 7]. Abnormal endometrial repair after injury results in the formation of intrauterine adhesions (IUA) and a thin endometrium, which are key causes for implantation failure and infertility. Umbilical cord-derived mesenchymal stem cells (UCMSCs) have been reported to repair the damaged endometrium. In the UCMSC-AAM group, the VEGF expression decreased, whereas that of MMP9 increased compared with the injury group. UCMSC transplantation using AAM as the carrier can be applied to treat endometrial injury in rats. The UCMSC-AAM complex may promote the better application of UCMSCs on the treatment of injured endometrium
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