Extracellular Vesicle‐Shuttled mRNA in Mesenchymal Stem Cell Communication

Mesenchymal stem cells (MSC) are multipotent cells able to differentiate into several cell types, hence providing cell reservoirs for therapeutic applications. The absence of detectable MSC homing at injury sites suggests that paracrine functions could, at least in part, be mediated by extracellular vesicles (EVs); EVs are newly identified players that are studied mainly as predictive or diagnostic biomarkers. Together with their clinical interests, EVs have recently come to the fore for their role in cell‐to‐cell communication. In this context, we investigated gene‐based communication mechanisms in EVs generated by bone marrow and umbilical cord blood MSC (BMMSC and CBMSC, respectively). Both MSC types released vesicles with similar physical properties, although CBMSC were able to secrete EVs with faster kinetics. A pattern of preferentially incorporated EV transcripts was detected with respect to random internalization from the cytosol, after a validated normalization procedure was established. In the paradigm where EVs act as bioeffectors educating target cells, we demonstrated that kidney tubular cells lacking IL‐10 expression and exposed to BMMSC‐EVs and CBMSC‐EVs acquired the IL‐10 mRNA, which was efficiently translated into the corresponding protein. These findings suggest that horizontal mRNA transfer through EVs is a new mechanism in the MSC restoring ability observed in vivo that is here further demonstrated in an in vitro rescue model after acute cisplatin injury of tubular cells. Stem Cells 2017;35:1093–1105 In the paradigm where extracellular vesicles play a role in cell‐to‐cell communication, we demonstrated that renal tubular cells, lacking IL‐10 expression and exposed to MSC IL‐10 mRNA‐containing EVs, acquired IL‐10 mRNA, which was then translated into the corresponding protein. Furthermore, MSC‐EVs were able to rescue cisplatin‐induced cell damage in an in vitro model of kidney acute injury.