Human Acellular Amniotic Matrix with Previously Seeded Umbilical Cord Mesenchymal Stem Cells Restores Endometrial Function in a Rat Model of Injury

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.

Identification and Verification of Five Potential Biomarkers Related to Skin and Thermal Injury Using Weighted Gene Co-Expression Network Analysis

“…However, whether MCEMP1 is associated with burn injury remains unclear. MMP9 is involved in the degradation of the ECM in BPs, such as reproduction ( Wang et al, 2021 ) and tissue remodeling ( Nandi et al, 2020 ). Burn injuries can trigger tissue changes that can explain the variation in the levels of different biochemical markers that can be recorded both locally and systemically.…”

MiR-455-5p upregulation in umbilical cord mesenchymal stem cells attenuates endometrial injury and promotes repair of damaged endometrium via Janus kinase/signal transducer and activator of transcription 3 signaling

“…UCMSCs, one of the best sources of MSCs, was once reported to ameliorate the severity of liver fibrosis [ 45 ]. Moreover, UCMSCs contribute to endometrial regeneration and repair [ 11 ]. In the present study, we cocultured ESCs with UCMSCs and confirmed that UCMSCs could promote the proliferation and cell cycle progression of ESCs and help to repair the damaged endometrium.…”

“…Compared to other kinds of MSCs, UCMSCs possess a superior capacity in differentiation, migration and self-renewal and can be invasively collected [ 10 ]. Increasing evidence has indicated that UCMSCs contribute to the repair of damaged endometrium [ 11 ]. For example, UCMSC transplantation restores endometrial thickness and attenuates excessive fibrosis in a rat model [ 12 ].…”

Future Challenges and Opportunities of Extracellular Matrix Hydrogels in Female Reproductive Medicine

“…ECM products that are obtained from decellularization of female reproductive organs have salient roles in the field of reproductive medicine, with research focusing mainly on those that are derived from the uterus [ 51 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ], ovary [ 50 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 ], cervix [ 93 ], vagina [ 94 , 95 ], and placenta [ 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 ]. The variable methods that are used for decellularization are dependent on the tissue type and its characteristics.…”

“…In situ cell delivery may improve treatments for diverse diseases. Compared to direct administration of cells or integration in ECM scaffolds [ 89 , 98 ], the use of hydrogels as carriers can enhance the rates of cell retention and cell engraftment in vivo [ 127 ]. Buckenmeyer patented an ovarian-derived hydrogel (OvaECM) for biomedical and biotechnology applications (US 2017/0252485 A1) and implemented it as a delivery system of follicles in a murine model of chemotherapy-induced POF [ 109 ].…”