Article (Scientific journals)
Dissecting the effects of preconditioning with inflammatory cytokines and hypoxia on the angiogenic potential of mesenchymal stromal cell (MSC)-derived soluble proteins and extracellular vesicles (EVs).
Gorgun, Cansu; Ceresa, Davide; Lesage, Raphaelle et al.
2021In Biomaterials, 269, p. 120633
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Keywords :
Cytokines; Extracellular Vesicles; Humans; Hypoxia; Inflammation; Mesenchymal Stem Cells; Angiogenesis; Extracellular vesicles; Mesenchymal stromal cells; Proteomics; RNASeq; Regenerative medicine
Abstract :
[en] Mesenchymal stromal cells (MSCs) are characterized by a regulatory phenotype and respond promptly to the environmental signals modulating their secretory activity. An appropriate preconditioning may induce MSCs to release secretomes with an enhanced regenerative potential. However, it fails to take into account that secretomes are composed by both soluble factors and extracellular vesicles (EVs), whose functions could be altered differently by the preconditioning approach. Here we demonstrate that the MSC secretome is strongly modulated by the simultaneous stimulation with hypoxia and pro-inflammatory cytokines, used to mimic the harsh environment present at the site of injury. We observed that the environmental variations strongly influenced the angiogenic potential of the different secretome fractions. Upon inflammation, the pro-angiogenic capacity of the soluble component of the MSC secretome was strongly inhibited, regardless of the oxygen level, while the EV-encapsulated component was not significantly affected by the inflammatory stimuli. These effects were accompanied by the modulation of the secreted proteins. On one hand, inflammation-activated MSCs release proteins mainly involved in the interaction with innate immune cells and in tissue remodeling/repair; on the other hand, when MSCs are not exposed to an inflamed environment, they respond to the different oxygen levels modulating the expression of proteins involved in the angiogenic process. The cargo content (in terms of miRNAs) of the corresponding EV fractions was less sensitive to the influence of the external stimuli. Our findings suggest that the therapeutic efficacy of MSC-based therapies could be enhanced by selecting the appropriate preconditioning approach and carefully discriminating its effects on the different secretome components.
Disciplines :
Engineering, computing & technology: Multidisciplinary, general & others
Author, co-author :
Gorgun, Cansu;  Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy,
Ceresa, Davide;  U.O. Cellular Oncology, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
Lesage, Raphaelle;  Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium,
Villa, Federico;  U.O. Cellular Oncology, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
Reverberi, Daniele;  U.O. Molecular Pathology, IRCCS Ospedale Policlinico, San Martino, Genova, Italy.
Balbi, Carolina;  Laboratory of Cellular and Molecular Cardiology, Cardiocentro Ticino Foundation,
Santamaria, Sara;  Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy.
Cortese, Katia;  Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy.
Malatesta, Paolo;  Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy,
Geris, Liesbet  ;  Université de Liège - ULiège > GIGA > GIGA In silico medecine - Biomechanics Research Unit ; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium,
Quarto, Rodolfo;  Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy,
Tasso, Roberta;  Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy,
Language :
English
Title :
Dissecting the effects of preconditioning with inflammatory cytokines and hypoxia on the angiogenic potential of mesenchymal stromal cell (MSC)-derived soluble proteins and extracellular vesicles (EVs).
Publication date :
February 2021
Journal title :
Biomaterials
ISSN :
0142-9612
eISSN :
1878-5905
Publisher :
Elsevier, Gb
Volume :
269
Pages :
120633
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
Available on ORBi :
since 29 June 2022

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