Engineering mesenchymal stem cells for premature ovarian failure: overcoming challenges and innovating therapeutic strategies

Premature ovarian failure (POF) is a leading cause of infertility in women, causing significant psychological and physical distress. Current therapeutic options are limited, necessitating the exploration of new treatments. Mesenchymal stem cells (MSCs), known for their remarkable homing and regenerative properties, have emerged as a promising intervention for POF. However, their clinical efficacy has been inconsistent. This paper aims to address these challenges by examining the cellular heterogeneity within MSC populations, which is crucial for identifying and selecting specific functional subpopulations for clinical applications. Understanding this heterogeneity can enhance therapeutic efficacy and ensure treatment stability. Additionally, this review comprehensively examines the literature on the effectiveness, safety, and ethical considerations of MSCs for ovarian regeneration, with a focus on preclinical and clinical trials. We also discuss potential strategies involving genetically and tissue-engineered MSCs. By integrating insights from these studies, we propose new directions for the design of targeted MSC treatments for POF and related disorders, potentially improving outcomes, addressing safety concerns, and expanding therapeutic options while ensuring ethical compliance.