We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Adipose Mesenchymal Extracellular Vesicles as Alpha-1-Antitrypsin Physiological Delivery Systems for Lung Regeneration.
- Authors
Bari, Elia; Ferrarotti, Ilaria; Di Silvestre, Dario; Grisoli, Pietro; Barzon, Valentina; Balderacchi, Alice; Torre, Maria Luisa; Rossi, Rossana; Mauri, Pierluigi; Corsico, Angelo Guido; Perteghella, Sara
- Abstract
Accumulating evidence shows that Mesenchymal Stem/Stromal Cells (MSCs) exert their therapeutic effects by the release of secretome, made of both soluble proteins and nano/microstructured extracellular vesicles (EVs). In this work, for the first time, we proved by a proteomic investigation that adipose-derived (AD)-MSC-secretome contains alpha-1-antitrypsin (AAT), the main elastase inhibitor in the lung, 72 other proteins involved in protease/antiprotease balance, and 46 proteins involved in the response to bacteria. By secretome fractionation, we proved that AAT is present both in the soluble fraction of secretome and aggregated and/or adsorbed on the surface of EVs, that can act as natural carriers promoting AAT in vivo stability and activity. To modulate secretome composition, AD-MSCs were cultured in different stimulating conditions, such as serum starvation or chemicals (IL-1β and/or dexamethasone) and the expression of the gene encoding for AAT was increased. By testing in vitro the anti-elastase activity of MSC-secretome, a dose-dependent effect was observed; chemical stimulation of AD-MSCs did not increase their secretome anti-elastase activity. Finally, MSC-secretome showed anti-bacterial activity on Gram-negative bacteria, especially for Klebsiella pneumoniae. These preliminary results, in addition to the already demonstrated immunomodulation, pave the way for the use of MSC-secretome in the treatment of AAT-deficiency lung diseases.
- Subjects
ELASTASES; ALPHA 1-antitrypsin; LUNG diseases; LUNGS; TREATMENT effectiveness; KLEBSIELLA pneumoniae; GRAM-negative bacteria
- Publication
Cells (2073-4409), 2019, Vol 8, Issue 9, p965
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells8090965