The role of human endometrial stem cells application in endometrial-factor induced infertility

Abstract

Background. Endometrial-factor induced infertility remains one of the most significant pathology among all fertility disorders. Stem cell-based therapy is considered to be the next-generation approach. However, at this point there are still issues about successfully retrieving human endometrium derived stem cells (hEnSCs). Moreover, we also need to establish a better understanding of the effect of hEnSCs on the endometrial recovery and the clinical outcome. Methods. Endometrium samples were collected from females undergoing assisted reproductive technology (ART) procedure due to couple infertility. These samples were obtained using an endometrium scratching. The hEnSCs were isolated from endometrium samples and characterized with flow cytometry analysis. Groups of endometrium injured female mice were established by the mechanical injury to uterine horns and the intraperitoneal chemotherapy. The hEnSCs suspension was injected to some of the studied female mice at approved time intervals. Morphological changes of mice uterine horns were evaluated after Masson‘s trichrome original staining and hematoxylin and eosin (H&E) staining. The fertility assessment of mice was performed by counting formed embryos. The expression of fibrosis related genes (Col1a1, Col3a1, Acta2 and CD44) was evaluated by the reverse transcription – quantitative polymerase chain reaction (RT-qPCR). Results. Endometrium scratching is an effective procedure for stem cells collection from human endometrium. Isolated hEnSCs met the criteria for defining mesenchymal stem cells (MSCs). Moreover, hEnSCs-based therapy had a demonstrably positive effect on the repair of damaged uterine horns layers, including a reduction of fibrosis, intensity of inflammatory cells such as lymphocytes and polymorphonuclear cells (PMNs) and the number of apoptotic bodies. The injured female mice had higher fertility after hEnSCs-based therapy in comparison to the untreated mice models. Gene expression was also reflected in morphology changes and outcomes of conception. Conclusions. hEnSCs demonstrated a positive impact on endometrium restoration and outcomes of endometrial-factor induced infertility. Further exploration is required in order to continue exploring the multifactorial associations between stem cell therapy, gene expression, endometrial changes and reproductive health, so we can identify individually effective and safe treatment strategies for endometrial-factor induced infertility, which is caused by mechanical effect or chemotherapy, in daily clinical practise.