Potential of bone marrow mesenchymal stem cell supernatant as a novel antifungal and antibiofilm agent against clinical Candida species isolates in vulvovaginal candidiasis

Vulvovaginal candidiasis (VVC) is a frequent fungal infection in women of reproductive age, primarily caused by Candida albicans and non-albicans Candida (NAC) species. The growing resistance to fluconazole (FLZ) and biofilm formation contribute to persistent and recurrent infections. Therefore, novel therapeutic strategies targeting resistant strains and biofilms are urgently needed. This study aimed to determine the prevalence of VVC, identify Candida species, assess FLZ resistance, and evaluate the antifungal and antibiofilm activities of bone marrow mesenchymal stem cell-derived supernatant (SBMMSC). From 2024 to 2025, 438 clinical samples from patients suspected of VVC were analyzed. Candida isolates were identified by culture and multiplex PCR. FLZ susceptibility was assessed using disk diffusion, and MIC values were determined for FLZ-resistant isolates (FLZ-RI). The antifungal and antibiofilm effects of SBMMSC and its impact on ALS3 and ERG11 gene expression were evaluated using qRT-PCR. A total of 106 VVC cases were confirmed, yielding 116 Candida isolates. C. albicans was the predominant species, accounting for 68 isolates (58.6%), while 48 isolates (41.4%) belonged to NAC species. Based on the disk diffusion assay, 30 of the 116 Candida isolates (25.9%) were classified as FLZ-RI. SBMMSC exhibited dose-dependent antifungal activity against FLZ-RI, inhibited biofilm formation in 91.4% of strains, and significantly downregulated ERG11 and ALS3 expression ( P < 0.05–0.0001). SBMMSC demonstrated promising antifungal and antibiofilm activities against FLZ-RI and reduced ERG11 and ALS3 expression. These findings suggest that SBMMSC may represent a promising candidate for further investigation in the management of resistant vulvovaginal candidiasis. However, cytotoxicity, biocompatibility, and in vivo efficacy were not evaluated in the present study. Therefore, further studies are required to assess its safety, therapeutic efficacy, and clinical applicability before translation into clinical practice.