Mesenchymal stem cell-based therapeutic strategies for female infertility: current evidence and emerging targeting approaches.

Abstract

Reproductive disorders remain a major cause of subfertility and infertility in human and animals, encompassing ovarian dysfunction, endometritis, impaired endometrial receptivity, and treatment-induced gonadotoxicity. These conditions substantially reduce reproductive efficiency and quality of life. In recent years, advances in translational medicine have shifted focus toward regenerative strategies, particularly stem cell-based therapies, as alternatives to conventional pharmacological or surgical interventions that often yield limited or transient benefits. Among these, mesenchymal stem/stromal cells (MSCs) have emerged as promising candidates for infertility management due to their self-renewal ability, multilineage differentiation potential, low immunogenicity, and robust paracrine activity. Growing preclinical and early clinical evidence demonstrates that MSC-based therapies can restore ovarian function, enhance folliculogenesis, promote endometrial regeneration, and modulate inflammatory and fibrotic microenvironments associated with female infertility. Notably, these effects are mediated primarily through the secretion of bioactive factors, stimulation of angiogenesis, regulation of apoptosis, and immunomodulation rather than direct cell replacement alone. Despite their therapeutic promise, challenges related to targeted delivery, therapeutic precision, and safety remain. In this context, emerging targeting strategies, particularly aptamer-based approaches, represent a rational advancement to enhance MSC efficacy. Aptamers are short single-stranded DNA or RNA molecules with high affinity and specificity for target proteins, offering advantages over antibodies, including improved tissue penetration, minimal immunogenicity, and ease of synthesis and modification. This review aimes to summarizes current progress in MSC-based therapies for female infertility and highlights aptamer-guided targeting strategies to improve therapeutic precision, efficacy, and safety.