Stem Cell-Based Regenerative Therapy for Genitourinary Syndrome of Menopause (GSM): Current Evidence and Future Perspectives

Genitourinary syndrome of menopause (GSM) is a common hypoestrogenic condition marked by vulvovaginal atrophy and lower urinary tract symptoms that significantly impair quality of life in peri- and postmenopausal women. Although local estrogen therapy remains the standard of care, its use is constrained by contraindications, adherence challenges, and concerns regarding long-term safety, particularly in women with estrogen-sensitive conditions. As a result, interest has grown in regenerative, non-hormonal alternatives. Stem cell-based therapy, particularly using mesenchymal stem cells (MSCs), has emerged as a potential therapeutic strategy for restoring urogenital tissue structure and function. The current body of evidence largely consists of preclinical studies, small clinical case series, and investigations in related but distinct conditions, which provide potential mechanistic insights. Preclinical studies suggest that MSCs from adipose tissue, bone marrow, and umbilical cord promote vaginal epithelial regeneration through paracrine mechanisms, including angiogenesis, immunomodulation, extracellular matrix remodeling, and restoration of local estrogen signaling and vaginal microbiota. To date, current clinical studies have not provided direct evidence on the efficacy of characterized MSC-based therapies specifically in GSM populations. Early clinical evidence, primarily involving adipose-derived tissue products such as micro-fragmented adipose tissue, reports improvements in symptoms overlapping with GSM, including vaginal dryness, dyspareunia, urinary symptoms, and sexual function, with benefits lasting up to two to three years after a single treatment and no serious adverse events reported. However, available data are limited by small cohorts, the absence of randomized trials, and regulatory variability. This review summarizes current evidence and outlines key scientific, ethical, and regulatory challenges that must be addressed to guide future research and clarify the therapeutic potential of MSC-based approaches in GSM, ultimately enabling translation.