Mesenchymal Stromal Cell Therapy for Premature Ovarian Insufficiency: Mechanisms and Perspectives.

Premature ovarian insufficiency (POI) is a clinically heterogeneous disorder characterized by ovarian dysfunction occurring before the age of 40, leading to infertility and increased long-term health risks. Current management strategies alleviate symptoms but fail to restore ovarian function or fertility, thereby prompting an urgent demand for regenerative therapies for POI. Mesenchymal stromal cells (MSCs) have emerged as a promising regenerative strategy due to their multifunctional capabilities, including paracrine effects, immunomodulation, and cytoprotection effects. This review systematically synthesizes preclinical and clinical evidence supporting the efficacy of MSCs in mitigating ovarian damage, enhancing folliculogenesis, restoring hormonal balance, and promoting the restoration of fertility in both POI models and patients. In addition, this article examines ongoing challenges, such as cellular heterogeneity, the determination of optimal transplantation strategies, and ensuring long-term safety. It also highlights innovative approaches, including biomaterial-enhanced transplantation, genetic engineering, and exosome-based therapies. The integration of these advanced strategies within personalized medicine frameworks holds significant potential to transform the clinical management of POI.