Chitosan microspheres loaded with WJMSCs facilitate the restoration of ovarian function in CTX-induced premature ovarian failure mice

Abstract

Premature ovarian failure (POF) is a complex disease affecting an increasing number of young women. Traditional treatments are limited in low efficacy and side effects. Wharton's jelly mesenchymal stem cells (WJMSCs) therapy holds promise in the treatment of POF. However, the clinical application of WJMSCs is hindered by challenges such as low cell viability, significant loss, and poor survival rates. In this study, we prepared three-dimensional chitosan microspheres (CSM). CSM loading substantial improved the proliferative ability and cell viability of WJMSCs. Furthermore, transplantation of CSM loaded with WJMSCs into ovaries of POF mice increased serum levels of Estradiol (E2) and Anti-Müllerian hormone (AMH), alongside decreased levels of follicle-stimulating hormone (FSH). CSM+WJMSCs transplantation enhanced the number of growth follicles while reduced atresia follicles, and effective alleviated the ovarian fibrosis and apoptosis within the ovarian cortex. CSM also prolonged the residence time of WJMSCs in the ovarian capsule. Moreover, superovulation experiments illustrated that CSM+WJMSCs transplantation enhanced the total number of oocytes and reduced oocyte abnormality rates. Overall, CSM+WJMSCs transplantation promotes follicle development and regeneration, restoring ovarian function by inhibiting ovarian cell apoptosis and reducing levels of fibrosis. This study presents a novel therapeutic strategy that combines biomaterial and mesenchymal stem cells for the clinical treatment of premature ovarian failure.