Interactions Between Mesenchymal Stem Cells and Microorganisms: Unraveling the Paradox for Enhanced Mesenchymal Stem Cell-Based Therapy

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic tool in stem cell-based therapy due to their immunomodulatory or regenerative characteristics. Nowadays, controlled application of nonpathogenic bacterial cells and their derivatives has shown promise in preconditioning and manipulating MSC behavior. This approach is being explored in various fields, including immunotherapy, tissue engineering, and cell therapy. However, recent discoveries have elucidated the complex interactions between MSCs and microorganisms, especially bacteria and viruses, raising concerns regarding the utility of MSCs in clinical applications. In this review, we discussed the interactions between MSCs and microorganisms and highlighted both positive and negative aspects. We also examined the use of bacterial-derived compounds in MSCs-mediated interventions. The balanced colonization of the microbiome in organs, such as the oral cavity, not only does not hinder therapeutic interventions but also could be crucial for achieving desirable outcomes. On the contrary, disturbances in the microbiome have been found to disturb the biological potential of MSCs, such as migration, osteogenic differentiation, and cell proliferation. Evidence also suggests that commensal bacteria, following certain interventions, can transition to a pathogenic state when interacting with MSCs, leading to acute inflammation. Indeed, the maintenance of homeostasis through various approaches, such as probiotic application, results in an optimal equilibrium during MSCs-based therapies. However, further investigation into this matter is imperative to identify efficacious interventions. Impact Statement This article will allow researchers to understand the approaches for manipulating the potential of bacteria and bacterial derivatives to help medical fields studying mesenchymal stem cells (MSCs), as well as handling the undesirable mutual effects of dysregulated microbiome and MSCs on their respective biological potentials.