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

1
Department of Medical Sciences and Molecular Biotechnology Center, University of Torino, 10126 Torino, Italy
2
Department of Biomedical Sciences and Paediatric Research Institute “Citta della Speranza”, University of Padova, 35129 Padova, Italy
3
2i3T Società per la gestione dell’incubatore di imprese e per il trasferimento tecnologico Scarl, University of Torino, 10126 Torino, Italy
4
Department of Molecular Biotechnology and Health Sciences and Molecular Biotechnology Center, University of Torino, 10126 Torino, Italy
5
Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, Rhode Island, RI 02912, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(10), 2381; https://doi.org/10.3390/ijms20102381
Received: 1 April 2019 / Revised: 10 May 2019 / Accepted: 10 May 2019 / Published: 14 May 2019
(This article belongs to the Special Issue Kidney Inflammation, Injury and Regeneration)
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Abstract

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. View Full-Text
Keywords: mesenchymal stromal cells; extracellular vesicles; acute kidney injury; modified-MSCs; microRNA mesenchymal stromal cells; extracellular vesicles; acute kidney injury; modified-MSCs; microRNA
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Tapparo, M.; Bruno, S.; Collino, F.; Togliatto, G.; Deregibus, M.C.; Provero, P.; Wen, S.; Quesenberry, P.J.; Camussi, G. Renal Regenerative Potential of Extracellular Vesicles Derived from miRNA-Engineered Mesenchymal Stromal Cells. Int. J. Mol. Sci. 2019, 20, 2381.

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