Beyond Antibiotics: MSC-Derived Secretome in Modulating Bacterial Viability, Biofilm Dynamics, and Resistance Gene Expression

Ajeng Destian Suparwi, Endang Purwaningsih, Nunung Ainur Rahmah, Eko setiawan

Abstract

Introduction: Antimicrobial resistance (AMR), particularly in biofilm-associated and chronic infections, has exposed critical limitations of conventional antibiotics. Biofilms enhance bacterial persistence through structural protection, metabolic adaptation, and regulated resistance mechanisms, necessitating alternative therapeutic strategies. Mesenchymal stem cell (MSC)–derived secretomes have emerged as a promising cell-free antimicrobial platform capable of modulating both bacterial behavior and host responses.

Methods: A narrative review was conducted using PubMed, Google Scholar, and GARUDA databases to identify studies evaluating antimicrobial, antibiofilm, and resistance-modifying effects of MSC-derived secretomes. Eligible studies included in vitro, ex vivo, and preclinical models assessing bacterial viability, biofilm dynamics, and resistance-associated pathways. Due to methodological heterogeneity, findings were qualitatively synthesized.

Results: The literature search identified 4,949 potentially relevant articles from PubMed, Google Scholar, and GARUDA databases. After duplicate removal and eligibility screening, 13 studies met the inclusion criteria and were included in the qualitative synthesis. The selected studies demonstrated that MSC-derived secretomes suppress bacterial growth, disrupt biofilm formation and mature biofilm stability, restore antibiotic susceptibility in tolerant populations, and modulate resistance-associated gene expression. Key antimicrobial components included antimicrobial peptides, extracellular vesicles, cysteine proteases, and immunomodulatory mediators that exert both direct antibacterial and host-mediated regulatory effects.

Conclusion: MSC derived secretomes act as systems-level antimicrobial modulators rather than conventional bactericidal agents. By targeting bacterial viability, biofilm architecture, resistance pathways, and host immunity simultaneously, they represent a promising adjunctive strategy for managing biofilm-driven and drug-resistant infections in the post-antibiotic era.

Keywords

antimicrobial; biofilm; mesenchymal stem cell; secretome

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DOI: https://doi.org/10.13057/smj.v9i1.115821

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