Renal Regenerative Potential of Extracellular Vesicles Derived from miRNA-Engineered Mesenchymal Stromal Cells

• Main Authors: Marta Tapparo, Stefania Bruno, Federica Collino, Gabriele Togliatto, Maria Chiara Deregibus, Paolo Provero, Sicheng Wen, Peter J. Quesenberry, Giovanni Camussi
• Format: Article
• Language: English
• Published: MDPI AG 2019-05-01
• Series: International Journal of Molecular Sciences
• Subjects: mesenchymal stromal cells; extracellular vesicles; acute kidney injury; modified-MSCs; microRNA
• Online Access: https://www.mdpi.com/1422-0067/20/10/2381

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) possess pro-regenerative potential in different animal models with renal injury. EVs contain different molecules, including proteins, lipids and nucleic acids. Among the shuttled molecules, miRNAs have a relevant role in the pro-regenerative effects of EVs and are a promising target for therapeutic interventions. The aim of this study was to increase the content of specific miRNAs in EVs that are known to be involved in the pro-regenerative effect of EVs, and to assess the capacity of modified EVs to contribute to renal regeneration in in vivo models with acute kidney injuries. To this purpose, MSCs were transiently transfected with specific miRNA mimics by electroporation. Molecular analyses showed that, after transfection, MSCs and derived EVs were efficiently enriched in the selected miRNAs. In vitro and in vivo experiments indicated that EVs engineered with miRNAs maintained their pro-regenerative effects. Of relevance, engineered EVs were more effective than EVs derived from naïve MSCs when used at suboptimal doses. This suggests the potential use of a low amount of EVs (82.5 × 10⁶) to obtain the renal regenerative effect.