The mechanisms of cellular crosstalk between mesenchymal stem cells and natural killer cells: Therapeutic implications

Mesenchymal stem cells (MSCs) are mesenchymal precursors of various origins, with well-known immunomodulatory effects. Natural killer (NK) cells, the major cells of the innate immune system, are critical for the antitumor and antiviral defenses; however, in certain cases, they may be the main culprits in the pathogenesis of some NK-related conditions such as autoimmunities and hematological malignancies. On the other hand, these cells seem to be the major responders in beneficial phenomena like graft versus leukemia. Substantial data suggest that MSCs can variably affect NK cells and can be affected by these cells. Accordingly, acquiring a profound understanding of the crosstalk between MSCs and NK cells and the involved mechanisms seems to be a necessity to develop therapeutic approaches based on such interactions. Therefore, in this study, we made a thorough review of the existing literature on the interactions between MSCs and NK cells with a focus on the underlying mechanisms. The current knowledge herein suggests that MSCs possess a great potential to be used as tools for therapeutic targeting of NK cells in disease context and that preconditioning of MSCs, as well as their genetic manipulation before administration, may provide a wider variety of options in terms of eliciting more specific and desirable therapeutic outcomes. Nevertheless, our knowledge regarding the effects of MSCs on NK cells is still in its infancy, and further studies with well-defined conditions are warranted herein.