Collagen Scaffold with Human Umbilical Cord Mesenchymal Stem Cells Remarkably Improves Intrauterine Adhesions in a Rat Model

Abstract

Background: Intrauterine adhesion (IUA) is the second leading cause of secondary infertility in women. Research has shown that stem cells can promote endometrial regeneration and that biomaterials are also helpful in tissue regeneration. Therefore, we compared the efficacy of a collagen scaffold combined with either human umbilical cord mesenchymal stem cells (hUCMSC) or estrogen for the treatment of IUA. Methods: The IUA-induced rats were injected with hUCMSCs or estrogen, and with a collagen scaffold. The endometrial glands and amount of fibrosis were assessed using hematoxylin and eosin and Masson staining. The extent of fibrosis and levels of regeneration-related cytokines were examined by real-time quantitative PCR, and the expression levels of the estrogen receptor, KI67 and cytokeratin were analyzed using an immunochemistry assay. In addition, human nuclear antigen (HuNu) and vimentin were examined by immunofluorescence microscopy. Results: The collagen scaffold administered with hUCMSCs markedly increased the number of endometrial glands and reduced the area of fibrosis compared with either the collagen scaffold or hUCMSCs alone. In addition, the collagen scaffold with hUCMSCs significantly regulated the expression levels of fibrosis, estrogen, and differentiation-related genes relative to the collagen scaffold or hUCMSCs alone. Furthermore, the hUCMSCs alone or in combination with the collagen scaffold increased the expression of HuNu and vimentin in the IUA-induced rat model. In addition, protein levels of the p-transcriptional co-activator with PDZ-binding motif, stromal cell-derived factor-1, and C-X-C chemokine receptor type 4 were upregulated in the group that received the collagen scaffold in combination with ­hUCMSCs. Conclusion: Our results suggest that the combination of the collagen scaffold with hUCMSCs may be an alternative approach for treating IUA.

Extracorporeal Shock Wave Therapy Combined with Platelet-Rich Plasma during Preventive and Therapeutic Stages of Intrauterine Adhesion in a Rat Model

“…These strategies afforded limited effects in alleviating endometrial fibrosis and inhibiting adhesion reformation, especially in severe IUA. Therefore, intrauterine injection of hyaluronic acid colloids, amniotic membrane transplantation, and stem cell therapy have been employed [ 71 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ]. Treatment with human umbilical cord mesenchymal stem cell-extracellular vesicles (UCMSC-EVs) alone or combined with estrogen significantly decreased not only inflammatory cytokines, such as TNF-α and IL-6, but also fibrosis markers, such as TGF-β, COL1α1, and VEGF.…”

Recent Advances in Understandings Towards Pathogenesis and Treatment for Intrauterine Adhesion and Disruptive Insights from Single-Cell Analysis

“…Many studies have confirmed that transplantation of bone marrow-derived stem cells, hematopoietic stem/progenitor cells, endometrial MSCs, embryonic stem cells, amniotic MSCs, and blood-derived stem cells can effectively promote the endometrial regeneration and menstrual recovery of IUA animal models or patients [84][85][86]. To improve the endometrial receptivity and improve the therapeutic effect of stem cell transplantation, Zhang et al [87] combined platelet-rich plasma (PRP) and blood-derived stromal cells in the IUA rat model in order to explore the therapeutic mechanisms.…”

Applications of Hydrogels in Premature Ovarian Failure and Intrauterine Adhesion

“…MSCs secrete a variety of cytokines (e.g., VEGF-A, TGF-β1, FGF-2) to promote glandular and vascular growth and degradation of fibrous scars (Ding et al, 2014;Xin et al, 2019;. Collagen increases the number of endometrial glands and endometrial thickness, reduces the area of fibrosis and improves pregnancy rates in a rat model (Ding et al, 2014;Liu et al, 2020). Compared with collagen alone, combining hUCMSCs more significantly increased the number of glands and reduced the area of fibrosis (Liu et al, 2020), and combining BMSCs was more effective in improving pregnancy rates, as well as in myometrium recovery and revascularization (Ding et al, 2014).…”