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.
Cell Factory, Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Enrico
E
Ragni
Cell Factory, Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Federica
F
Banfi
Cell Factory, Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.|Department of Industrial Engineering, University of Padova, Padova, Italy.
Mario
M
Barilani
Cell Factory, Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Alessandro
A
Cherubini
Cell Factory, Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Valentina
V
Parazzi
Autoimmunity Program, Istituto Nazionale di Genetica Molecolare "Romeo Ed Enrica Invernizzi", Milan, Italy.|Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Paola
P
Larghi
Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
Vincenza
V
Dolo
EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy.|Epidemiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Valentina
V
Bollati
Cell Factory, Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Lorenza
L
Lazzari
D020413:3' Untranslated Regions / Q000235:genetics; D002450:Cell Communication; D000067128:Extracellular Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000648:ultrastructure; D008954:Models, Biological; D009930:Organic Chemicals / Q000378:metabolism; D014176:Protein Biosynthesis; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D013194:Staining and Labeling; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; D009930:Organic Chemicals; C070080:PKH 26; D012333:RNA, Messenger; D016753:Interleukin-10
Extracellular vesicles; IL-10; Mesenchymal stem cells; mRNA