TY - JOUR
T1 - Therapeutic effects of adipose-tissue-derived mesenchymal stromal cells and their extracellular vesicles in experimental silicosis
AU - Bandeira, Elga
AU - Oliveira, Helena
AU - Silva, Johnatas D.
AU - Menna-Barreto, Rubem F.S.
AU - Takyia, Christina M.
AU - Suk, Jung S.
AU - Witwer, Kenneth W.
AU - Paulaitis, Michael E.
AU - Hanes, Justin
AU - Rocco, Patricia R.M.
AU - Morales, Marcelo M.
N1 - Funding Information:
This study was supported by the Brazilian Council for Scientific and Technological Development (CNPq), the Rio de Janeiro State Research Foundation (FAPERJ), the Department of Science and Technology (DECIT)/ Brazilian Ministry of Health, the Coordination for the Improvement of Higher Education Personnel (CAPES), and National Institute of Science and Technology for Regenerative Medicine.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/5/29
Y1 - 2018/5/29
N2 - Background: Silicosis is an occupational disease that affects workers who inhale silica particles, leading to extensive lung fibrosis and ultimately causing respiratory failure. Mesenchymal stromal cells (MSCs) have been shown to exert therapeutic effects in lung diseases and represent an alternative treatment for silicosis. Recently, it has been suggested that similar effects can be achieved by the therapeutic use of extracellular vesicles (EVs) obtained from MSCs. The aim of this study was to investigate the effects of adipose-tissue-derived MSCs (AD-MSCs) or their EVs in a model of silicosis. Methods: Silicosis was induced by intratracheal instillation of silica in C57BL/6 mice. After the onset of disease, animals received saline, AD-MSCs, or EVs, intratracheally. Results: At day 30, AD-MSCs and EVs led to a reduction in collagen fiber content, size of granuloma, and in the number of macrophages inside granuloma and in the alveolar septa. In addition, the expression levels of interleukin 1β and transforming growth factor beta in the lungs were decreased. Higher dose of EVs also reduced lung static elastance when compared with the untreated silicosis group. Conclusions: Both AD-MSCs and EVs, locally delivered, ameliorated fibrosis and inflammation, but dose-enhanced EVs yielded better therapeutic outcomes in this model of silicosis.
AB - Background: Silicosis is an occupational disease that affects workers who inhale silica particles, leading to extensive lung fibrosis and ultimately causing respiratory failure. Mesenchymal stromal cells (MSCs) have been shown to exert therapeutic effects in lung diseases and represent an alternative treatment for silicosis. Recently, it has been suggested that similar effects can be achieved by the therapeutic use of extracellular vesicles (EVs) obtained from MSCs. The aim of this study was to investigate the effects of adipose-tissue-derived MSCs (AD-MSCs) or their EVs in a model of silicosis. Methods: Silicosis was induced by intratracheal instillation of silica in C57BL/6 mice. After the onset of disease, animals received saline, AD-MSCs, or EVs, intratracheally. Results: At day 30, AD-MSCs and EVs led to a reduction in collagen fiber content, size of granuloma, and in the number of macrophages inside granuloma and in the alveolar septa. In addition, the expression levels of interleukin 1β and transforming growth factor beta in the lungs were decreased. Higher dose of EVs also reduced lung static elastance when compared with the untreated silicosis group. Conclusions: Both AD-MSCs and EVs, locally delivered, ameliorated fibrosis and inflammation, but dose-enhanced EVs yielded better therapeutic outcomes in this model of silicosis.
KW - Extracellular vesicles
KW - Fibrosis
KW - Inflammation
KW - Mesenchymal stromal cells
KW - Silicosis
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U2 - 10.1186/s12931-018-0802-3
DO - 10.1186/s12931-018-0802-3
M3 - Article
C2 - 29843724
AN - SCOPUS:85047723251
SN - 1465-9921
VL - 19
JO - Respiratory research
JF - Respiratory research
IS - 1
M1 - 104
ER -