دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Adipose Mesenchymal Extracellular Vesicles as Alpha-1-Antitrypsin Physiological Delivery Systems for Lung Regeneration
المؤلفون: Bari E, Ferrarotti I, Di Silvestre D, Grisoli P, Barzon V, Balderacchi A, Torre ML, Rossi R, MAURI, PAOLO, Corsico AG, Perteghella S
المساهمون: Bari, E, Ferrarotti, I, Di Silvestre, D, Grisoli, P, Barzon, V, Balderacchi, A, Torre, Ml, Rossi, R, Mauri, Paolo, Corsico, Ag, Perteghella, S
سنة النشر: 2019
المجموعة: Università degli Studi del Piemonte Orientale: CINECA IRIS
الوصف: 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.
نوع الوثيقة: article in journal/newspaper
اللغة: English
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/31450843; info:eu-repo/semantics/altIdentifier/wos/WOS:000489103800024; volume:23; issue:8; journal:CELLS; http://hdl.handle.net/11579/133243Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85077049525
DOI: 10.3390/cells8090965
الإتاحة: https://doi.org/10.3390/cells8090965Test
http://hdl.handle.net/11579/133243Test
حقوق: info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.2DAEE660
قاعدة البيانات: BASE