Vulvovaginal candidiasis, a common fungal infection affecting women of reproductive age, may be facing a new kind of biological countermeasure. Researchers from institutions in Iran and Austria report that a cell-free preparation derived from bone marrow mesenchymal stem cells showed antifungal and antibiofilm activity against clinical Candida isolates, including strains classified as resistant to fluconazole, one of the most widely used treatments for the infection. The study, published in BMC Infectious Diseases, investigated whether the liquid surrounding cultured mesenchymal stem cells could suppress Candida growth and interfere with the molecular machinery that helps the fungus attach to surfaces and establish persistent biofilms.
The investigation focused on a major clinical problem in vulvovaginal candidiasis: infections that return repeatedly or fail to respond to standard azole therapy. Candida albicans remains the dominant cause of the disease, but non-albicans Candida species are increasingly recognized in recurrent and treatment-resistant cases. These organisms can differ in their intrinsic susceptibility to antifungal drugs, while some acquire resistance after repeated exposure. Biofilms add another layer of difficulty. A biofilm is a structured microbial community enclosed within a protective extracellular matrix. In Candida, this organization can reduce drug penetration, alter fungal metabolism, and create a reservoir of cells that survive treatment more effectively than free-floating yeast cells.
Between 2024 and 2025, the research team analyzed 438 clinical samples collected from patients suspected of having vulvovaginal candidiasis. Laboratory testing confirmed 106 cases and yielded 116 Candida isolates, indicating that some samples contained more than one isolate or that multiple strains were recovered during the investigation. Species identification was performed through culture-based methods and multiplex polymerase chain reaction, a molecular technique that uses several targeted DNA amplification reactions in parallel to distinguish organisms based on species-specific genetic sequences. Of the isolates, 68, or 58.6 percent, were identified as C. albicans. The remaining 48 isolates, representing 41.4 percent, belonged to non-albicans Candida species.
The researchers next assessed susceptibility to fluconazole using disk diffusion testing, in which fungal growth around a drug-containing disk is measured to estimate sensitivity. Thirty of the 116 isolates, equivalent to 25.9 percent, were categorized as fluconazole-resistant. For these resistant isolates, the investigators determined minimum inhibitory concentrations, or MIC values. The MIC is the lowest concentration of a compound that visibly prevents microbial growth under defined laboratory conditions. Although MIC testing provides a more quantitative measure than a basic screening assay, it remains an in vitro result and does not automatically predict how a treatment will perform in a patient, where drug distribution, tissue conditions, immune responses, and the vaginal microbiome can all influence outcomes.
The experimental agent was bone marrow mesenchymal stem cell-derived conditioned medium, referred to in the study as SBMMSC. Mesenchymal stem cells are multipotent stromal cells that can release a broad mixture of biologically active molecules, including cytokines, chemokines, growth factors, extracellular vesicles, and other soluble mediators. Conditioned medium is the fluid collected after cells have been cultured, allowing researchers to study the substances secreted by the cells without administering the living cells themselves. This distinction is important. A cell-free supernatant may be easier to standardize and could avoid some of the safety and manufacturing challenges associated with transplanting viable stem cells, but its composition can vary according to the source of the cells, culture conditions, collection time, and processing methods.
In laboratory experiments, SBMMSC displayed dose-dependent antifungal activity against the fluconazole-resistant isolates. In practical terms, stronger concentrations of the conditioned medium produced greater inhibition of fungal growth, although the study’s abstract does not provide the complete concentration-response data or identify a single universal active molecule responsible for the effect. The findings suggest that the supernatant contains one or more secreted factors capable of disrupting Candida physiology. These factors might affect the fungal cell membrane, interfere with metabolic pathways, alter stress responses, or act through several mechanisms at once. Further chemical and proteomic analyses will be required to determine which components are active, whether they work synergistically, and whether their activity can be reproduced consistently in a pharmaceutical formulation.
The researchers also examined the effect of SBMMSC on Candida biofilms. The conditioned medium inhibited biofilm formation in 91.4 percent of the strains tested, a result that places the antibiofilm activity at the center of the study’s potential significance. Preventing a biofilm from forming is not the same as eradicating a mature biofilm. Early intervention may block adhesion, filamentation, cell-to-cell communication, or production of the extracellular matrix, whereas established biofilms can display substantially greater tolerance to antifungal treatment. The available findings therefore support the idea that SBMMSC interferes with biofilm development, but they do not yet demonstrate that it can reliably remove mature Candida biofilms or cure an established infection in living tissue.
To explore possible molecular effects, the investigators measured expression of two Candida genes using quantitative real-time polymerase chain reaction. The first, ALS3, encodes an agglutinin-like sequence protein associated with adhesion, interaction with host cells, and biofilm development. The second, ERG11, encodes lanosterol 14-alpha-demethylase, an enzyme involved in the ergosterol biosynthesis pathway. Ergosterol is a vital sterol in the fungal cell membrane and is a major target of azole drugs, including fluconazole. The study found that SBMMSC significantly downregulated expression of both ALS3 and ERG11, with reported statistical significance ranging from P less than 0.05 to P less than 0.0001. These changes are consistent with reduced adhesive capacity and impaired membrane-sterol production, but gene-expression changes alone do not prove that either pathway is the direct cause of fungal inhibition.
The results are promising because they point toward a possible complementary strategy for infections that are increasingly difficult to manage with conventional antifungals. A secretome-based treatment could, in principle, be developed as a topical agent for the vaginal environment, used alone, or combined with existing drugs to improve activity against resistant Candida and biofilm-associated disease. However, the study remains an early laboratory investigation. It did not evaluate cytotoxicity, biocompatibility, pharmacokinetics, effects on beneficial vaginal microorganisms, animal efficacy, or clinical outcomes. Those questions are particularly important for a potential vaginal therapy, where irritation, immune reactions, disruption of the normal microbiota, and local stability must all be carefully assessed. Before clinical translation, researchers will need to define the active components, establish manufacturing and quality-control standards, test the preparation against mature biofilms and diverse Candida species, and verify safety in appropriate cellular, animal, and human studies. For now, the findings indicate that mesenchymal stem cell supernatant is a candidate for further investigation—not yet a proven treatment for vulvovaginal candidiasis.
Subject of Research: Antifungal and antibiofilm activity of bone marrow mesenchymal stem cell-derived conditioned medium against clinical Candida isolates associated with vulvovaginal candidiasis.
Article Title: Potential of bone marrow mesenchymal stem cell supernatant as a novel antifungal and antibiofilm agent against clinical Candida species isolates in vulvovaginal candidiasis
Article References: Amirinia, F., Motamedi, M., Pourhajibagher, M. et al. “Potential of bone marrow mesenchymal stem cell supernatant as a novel antifungal and antibiofilm agent against clinical Candida species isolates in vulvovaginal candidiasis.” BMC Infectious Diseases (2026).
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DOI: 10.1186/s12879-026-14189-3
Keywords: Vulvovaginal candidiasis; Candida species; Candida albicans; non-albicans Candida; fluconazole resistance; antifungal agents; biofilm; bone marrow mesenchymal stem cells; conditioned medium; ALS3; ERG11; real-time PCR.
Tags: alternative therapies for recurrent vulvovaginal candidiasisantibiofilm effects in fungal infectionsantifungal activity against Candidaantifungal resistance in Candida speciesbiofilm disruption in vulvovaginal candidiasisbone marrow mesenchymal stem cell supernatantCandida biofilm molecular mechanismscell-free stem cell therapy for fungal infectionsnovel treatments for biofilm-associated fungal infectionsresistant Candida strains treatmentstem cell derived supernatants in infectious disease controlvaginal infections
