Next Article in Journal
Advances of Single-Cell Protein Analysis
Previous Article in Journal
Activated Cardiac Fibroblasts Control Contraction of Human Fibrotic Cardiac Microtissues by a β-Adrenoreceptor-Dependent Mechanism
Open AccessArticle

Secretome of Mesenchymal Stromal Cells Prevents Myofibroblasts Differentiation by Transferring Fibrosis-Associated microRNAs within Extracellular Vesicles

1
Institute for Regenerative Medicine, Medical Research and Educational Centre, Lomonosov Moscow State University, 119192 Moscow, Russia
2
Faculty of Medicine, Lomonosov Moscow State University, 119192 Moscow, Russia
3
Faculty of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia
*
Author to whom correspondence should be addressed.
Cells 2020, 9(5), 1272; https://doi.org/10.3390/cells9051272
Received: 21 April 2020 / Revised: 11 May 2020 / Accepted: 14 May 2020 / Published: 20 May 2020
Fibroblasts differentiation into myofibroblasts is a central event of tissue fibrosis. Multipotent mesenchymal stromal cells (MSCs) secretome can interfere with fibrosis development; despite precise underlying mechanisms remain unclear. In this study, we tested the hypothesis that MSC secretome can affect fibroblast’ differentiation into myofibroblasts by delivering regulatory RNAs, including microRNAs to these cells. Using the model of transforming growth factor-beta (TGFbeta)-induced fibroblast differentiation into myofibroblasts, we tested the activity of human MSC secretome components, specifically extracellular vesicles (MSC-EV). We showed that MSC-EV down-regulated secretion of extracellular matrix proteins by fibroblasts as well as suppressed their contractility resulting in prevention as well as reversion of fibroblasts differentiation to myofibroblasts. High-throughput sequencing of RNAs extracted from MSC-EV has revealed many fibrosis-associated microRNAs. Fibroblast treatment with MSC-EV led to direct transfer of microRNAs, which resulted in the elevation of most prominent fibrosis-associated microRNAs, including microRNA-21 and microRNA-29c. Using MSC-EV transfection by antagomirs to these microRNAs we demonstrated their involvement in the suppression of fibroblast differentiation in our model. Taken together, MSC secretome can suppress fibrosis by prevention of fibroblast differentiation into myofibroblasts as well as induce de-differentiation of the latter by direct transfer of specific microRNAs. View Full-Text
Keywords: mesenchymal stem/stromal cells; fibrosis; myofibroblasts; secretome; extracellular vesicles; microRNA mesenchymal stem/stromal cells; fibrosis; myofibroblasts; secretome; extracellular vesicles; microRNA
Show Figures

Figure 1

MDPI and ACS Style

Basalova, N.; Sagaradze, G.; Arbatskiy, M.; Evtushenko, E.; Kulebyakin, K.; Grigorieva, O.; Akopyan, Z.; Kalinina, N.; Efimenko, A. Secretome of Mesenchymal Stromal Cells Prevents Myofibroblasts Differentiation by Transferring Fibrosis-Associated microRNAs within Extracellular Vesicles. Cells 2020, 9, 1272.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop