Beyond Regeneration: Mesenchymal Stem Cells as Antimicrobial Agents in Burn Wound Healing

Abstract

Burn injuries present a considerable global health challenge, characterised by intricate healing processes that are exacerbated by infection and impaired tissue regeneration. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their regenerative, immunomodulatory, and antimicrobial properties. MSCs have been shown to secrete AMPs such as LL-37 and hepcidin, which have been found to directly target pathogens including Pseudomonas aeruginosa and Staphylococcus aureus. In addition to this direct antimicrobial action, MSCs have also been observed to modulate immune responses through the secretion of cytokines such as IL-10 and TGF-β. Their regenerative effects include the promotion of angiogenesis, re-epithelialization, and extracellular matrix (ECM) remodelling via growth factors such as EGF, KGF, and SDF-1. In-vitro and animal studies have demonstrated enhanced wound closure, reduced scarring, and improved antimicrobial efficacy through novel delivery systems such as hydrogels and preconditioning strategies. As demonstrated by clinical trials, the treatment has been shown to facilitate accelerated healing and reduced reliance on antibiotics. However, challenges such as the heterogeneity of mesenchymal stem cells (MSCs), optimisation of dosing, and safety concerns (e.g. coagulopathy, systemic inflammation) persist. Emerging technologies, including synthetic gene circuits, microbiome-targeted engineering, and bioresponsive delivery systems, offer solutions to enhance the efficacy of MSCs. This review emphasises the potential of MSCs to transform the management of burn wounds, while underscoring the necessity for standardised protocols and advanced engineering to surmount translational barriers.