ABSTRACT
Introduction: Cell transplantation is an emerging and effective therapeutic approach for enhancing uterine adhesions caused by endometrial damage. Currently, human umbilical cord blood mononuclear cells (HUCBMCs) have been extensively for tissue and organ regeneration. However, their application in endometrial repair remains unexplored. Our investigation focuses on the utilization of HUCBMCs for treating endometrial injury. Methods: The HUCBMCs were isolated from health umbilical cord blood, and co-cultured with the injured endometrial stromal cells and injured endometrial organoids. The cell proliferation and apoptosis were measured by cck8 assays and flow cytometry. Western blotting was used to detect the expression of PTEN, AKT and p-AKT. Immunofluorescence assay revealed expression levels of epithelial-mesenchymal transition (EMT) -related markers such as E-cadherin, N-cadherin, and TGF-ß1. The endometrial thickness, fibrosis level, and glandular number were examined after the intravenous injection of HUCBMCs in mouse endometrial models. Immunohistochemistry was employed to assess changes in growth factors vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) as well as fibrosis markers α-SMA and COL1A1. Additionally, expressions of EMT-related proteins E-cadherin and N-cadherin were evaluated. Results: HUCBMCs significantly improved the proliferation and reduced the apoptosis of damaged endometrial stromal cells (ESCs), accompanied by up-regulation of phospho-AKT expression. HUCBMCs increased endometrial thickness and glandular count while decreasing fibrosis and EMT-related markers in mouse endometrial models. Furthermore, EMT-related markers of ESCs and endometrial organoids were significantly decreased. Conclusions: Our findings suggest that HUCBMCs plays a pivotal role in mitigating endometrial injury through the attenuation of fibrosis. HUCBMCs may exert a reverse effect on the EMT process during the endometrium reconstruction.
ABSTRACT
Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in women of reproductive age. The PCOS leads to obesity, dyslipidemia, insulin resistance, hyperandrogenism, and infertility. We established an induced pluripotent stem cell line (iPSC) from a PCOS patient. This disease-specific iPSC line will be beneficial to study PCOS in vitro, allowing to understand the pathogenic mechanisms and a cell-based model for drug development for PCOS.
Subject(s)
Hyperandrogenism , Induced Pluripotent Stem Cells , Insulin Resistance , Polycystic Ovary Syndrome , Female , Humans , Induced Pluripotent Stem Cells/metabolism , Obesity , Polycystic Ovary Syndrome/metabolismABSTRACT
The human endometrial stromal cells (hEndoSCs) could maintain endometrial homeostasis and play a critical role in repairing endometrial injury. Mesenchymal stem cells (MSCs) significantly increase the proliferation of damaged hEndoSCs and protect them from apoptosis. Recent studies indicated that exosomes derived from stem cells could be recruited to damaged tissues for regeneration, which exhibit the potential for stem cell therapy as therapeutic vectors. In this study, we isolated human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) and investigated the effects of hUCMSC-Exos on mifepristone-induced hEndoSC injury. Exosome uptake and cell proliferation as well as cell apoptosis of damaged hEndoSCs treated with hUCMSC-Exos were detected. We also assessed the expression of apoptosis-related proteins and the PTEN/AKT signaling pathway. We found hUCMSC-Exos improved the proliferation of damaged hEndoSCs and protected hEndoSCs from the mifepristone-induced apoptosis. hUCMSC-Exos upregulated Bcl-2 level as well as downregulated Cleaved Caspase-3 level and activated the PTEN/AKT signaling pathway to regulate the proliferation and antiapoptosis. These results indicated hUCMSC-Exos protected hEndoSCs from mifepristone-induced apoptosis and played an active role in repairing the damaged hEndoSCs through the PTEN/AKT signaling pathway in vitro. hUCMSC-Exos may hold great promise in the cell-free therapy of endometrial injury.
