Exploring therapeutic avenues: mesenchymal stem/stromal cells and exosomes in confronting enigmatic biofilm-producing fungi

Abstract

Fungal infections concomitant with bioflms can demonstrate an elevated capacity to withstand substantially higher concentrations of antifungal agents, contrasted with infectious diseases caused by planktonic cells. This inherent resilience intrinsic to bioflm-associated infections engenders a formidable impediment to efective therapeutic interventions. The diferent mechanisms that are associated with the intrinsic resistance of Candida species encompass drug sequestration by the matrix, drug efux pumps, stress response cell density, and the presence of persister cells. These persisters, a subset of fungi capable of surviving hostile conditions, pose a remarkable challenge in clinical settings in virtue of their resistance to conventional antifungal therapies. Hence, an exigent imperative has arisen for the development of novel antifungal therapeutics with specifc targeting capabilities focused on these pathogenic persisters. On a global scale, fungal persistence and their resistance within bioflms generate an urgent clinical need for investigating recently introduced therapeutic strategies. This review delves into the unique characteristics of Mesenchymal stem/stromal cells (MSCs) and their secreted exosomes, which notably exhibit immunomodulatory and regenerative properties. By comprehensively assessing the current literature and ongoing research in this feld, this review sheds light on the plausible mechanisms by which MSCs and their exosomes can be harnessed to selectively target fungal persisters. Additionally, prospective approaches in the use of cell-based therapeutic modalities are examined, emphasizing the importance of further research to overcome the enigmatic fungal persistence.