Adipose Mesenchymal Extracellular Vesicles as Alpha-1-Antitrypsin Physiological Delivery Systems for Lung Regeneration

Elia Bari, Ilaria Ferrarotti, Dario Di Silvestre, Pietro Grisoli, Valentina Barzon, Alice Balderacchi, Maria Luisa Torre, Rossana Rossi, Pierluigi Mauri, Angelo Guido Corsico, Sara Perteghella

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Issue number9
Publication statusPublished - Aug 23 2019


  • *alpha-1-antitrypsin
  • *anti-elastase
  • *lung diseases
  • *mesenchymal exosomes
  • *mesenchymal extracellular vesicles
  • *mesenchymal microvesicles
  • *mesenchymal secretome


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