Nano-Enabled Stem Cell Therapy Ameliorates Premature Ovarian Failure in Rats via Hormonal and Follicular Regeneration

Background: Premature ovarian failure (POF), clinically referred to as primary ovarian insufficiency (POI), represents a loss of ovarian function occurring before the age of 40 and remains a major cause of infertility in young women. Existing therapeutic interventions provide limited benefit, highlighting the need for innovative regenerative strategies. Stem cell-based therapies combined with bioengineered nanomaterials have recently emerged as promising approaches to restore ovarian physiology and fertility. Materials and Methods: Cerium oxide (CeO2) nanoparticles were produced using an eco-friendly synthesis technique and were comprehensively characterized using SEM, EDX, FTIR, DLS, and zeta potential measurements. Unrestricted somatic stem cells (USSCs) were extracted from human umbilical cord blood. The therapeutic potential of CeO2 nanomaterials alone and in combination with USSCs was explored in a chemotherapy-induced POF rat model. Results: Physicochemical analysis confirmed spherical CeO2 nanoparticles with an average particle size of 10–30 nm and a surface charge of approximately +3 mV. In vitro assays demonstrated acceptable biocompatibility with minimal cytotoxicity up to 64 µg/mL. Notably, co-administration of CeO2 nanoparticles and USSCs in vivo resulted in marked ovarian recovery, reflected by improvement in reproductive hormone levels (FSH and E₂), increased ovarian index, and superior pregnancy success compared to individual treatments. Conclusion: The study demonstrates that green-synthesized CeO2 nanoparticles support stem cell-based ovarian repair and may represent a viable combined therapeutic approach for the management of premature ovarian failure.