Adipose-derived stem cells and adipose-derived stem cell-conditioned medium modulate in situ imbalance between collagen I-and collagen V-mediated IL-17 immune response recovering bleomycin pulmonary fibrosis

dc.contributor.authorFelix, Renato Goncalves [UNESP]
dc.contributor.authorCarvalho Bovolato, Ana Livia [UNESP]
dc.contributor.authorCotrim, Ondina Silvia [UNESP]
dc.contributor.authorLeao, Patricia dos Santos
dc.contributor.authorBatah, Sabrina Setembre
dc.contributor.authorGolim, Marjorie de Assis [UNESP]
dc.contributor.authorVelosa, Ana Paula
dc.contributor.authorTeodoro, Walcy
dc.contributor.authorMartins, Vanessa
dc.contributor.authorCruz, Fernanda Ferreira
dc.contributor.authorDeffune, Elenice [UNESP]
dc.contributor.authorFabro, Alexandre Todorovic
dc.contributor.authorCapelozzi, Vera Luiza
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal do Rio de Janeiro (UFRJ)
dc.date.accessioned2020-12-11T22:20:23Z
dc.date.available2020-12-11T22:20:23Z
dc.date.issued2020-03-01
dc.description.abstractThe immunogenic collagen V (Col V) and the proinflammatory cytokine interleukin (IL)-17 have been implicated in the pathogenesis of multiple autoimmune diseases. Col V is also up-regulated during adipogencsis and can stimulate adipocyte differentiation in vitro. Conditioned medium (CM) generated from adipose-derived mesenchymal stem cells (MSCs) reduces bleomycin (BLM)-induced lung injury in rats, suggesting a crucial role in situ of immunomodulatory factors secreted by MSCs in these beneficial effects. In the present work, we investigated this hypothesis, analyzing levels of plasma inflammatory mediators and inflammatory and fibrotic mediators in the lung tissue of BLM-injured rats after treatment with MSCs and CM. Pulmonary fibrosis was intratracheally induced by BLM. After 10 days, BLM animals were further randomized into subgroups receiving saline, MSCs, or CM intravenously. On days 14 and 21, the animals were euthanized, and the lungs were examined through protein expression of nitric oxide synthase (NOS), IL-17, transforming growth factor-beta (TGF-beta), vascular endothelial growth factor, endothelin-1, and the immunogenic Col V through histological quantitative evaluation and plasma levels of fibrinogen, Von Willebrand factor, and platelet-derived growth factor (PDGF). Rats that had been injected with MSCs and CM showed a significant increase in weight and significant improvements at 14 and 21 days after intravenous injection at both time points of analysis of plasma fibrinogen, PDGF, and Von Willebrand factor and NOS-2 expression, supporting an early anti-inflammatory action, thus reducing TGF-beta and collagen I fibers. In contrast, intravenous injection of CM was able to significantly increase the deposition of Col V fibers and IL-17 on both day 14 and day 21 as compared with the amount observed in rats from the BLM group and MSC groups. In conclusion, this study reinforces previous observations on the therapeutic properties of MSCs and CM and is the first report to demonstrate the association of its actions with immunomodulatory biomarkers on lung tissue. We concluded that adipose-derived stem cells and adipose-derived stem cells-CM modulate an in situ imbalance between collagen I- and Col V-mediated IL-17 immune response, emerging as a promising therapeutic option for recovering from BLM pulmonary fibrosis.en
dc.description.affiliationSao Paulo State Univ, Botucatu Med Sch, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Med, Rheumatol Div, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Med, Dept Pathol, Av Dr Arnaldo 455,Sala 1143, BR-01246903 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Lab Pulm Invest, Rio De Janeiro, RJ, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Botucatu Med Sch, Sao Paulo, Brazil
dc.description.sponsorshipNational Council for Scientific and Technological Development
dc.description.sponsorshipFoundation for the Support of Research of the State of Sao Paulo
dc.description.sponsorshipLaboratories for Medical Research [LIMs], Hospital das Clinicas, University of Sao Paulo
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIdNational Council for Scientific and Technological Development: CNPq-471939/2010-2
dc.description.sponsorshipIdNational Council for Scientific and Technological Development: 483005/2012-6
dc.description.sponsorshipIdFoundation for the Support of Research of the State of Sao Paulo: FAPESP 12/03543-2
dc.description.sponsorshipIdFoundation for the Support of Research of the State of Sao Paulo: FAPESP11/09181-2
dc.description.sponsorshipIdFoundation for the Support of Research of the State of Sao Paulo: FAPESP 2012/07040-5
dc.description.sponsorshipIdFoundation for the Support of Research of the State of Sao Paulo: FAPESP 2013/05886-7
dc.description.sponsorshipIdFoundation for the Support of Research of the State of Sao Paulo: FAPESP 2013/14277-4
dc.description.sponsorshipIdFoundation for the Support of Research of the State of Sao Paulo: FAPESP 2018/20403-6
dc.format.extent289-301
dc.identifierhttp://dx.doi.org/10.14670/HH-18-152
dc.identifier.citationHistology And Histopathology. Murcia: F Hernandez, v. 35, n. 3, p. 289-301, 2020.
dc.identifier.doi10.14670/HH-18-152
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/11449/197861
dc.identifier.wosWOS:000552623800007
dc.language.isoeng
dc.publisherF Hernandez
dc.relation.ispartofHistology And Histopathology
dc.sourceWeb of Science
dc.subjectAdipose-derived mesenchymal stem cells
dc.subjectConditioned medium
dc.subjectCollagen fibers
dc.subjectGrowth factors
dc.subjectCytokines
dc.subjectIL-17
dc.subjectBleomycin
dc.subjectCollagen V
dc.subjectElectron microscopy
dc.titleAdipose-derived stem cells and adipose-derived stem cell-conditioned medium modulate in situ imbalance between collagen I-and collagen V-mediated IL-17 immune response recovering bleomycin pulmonary fibrosisen
dc.typeArtigo
dcterms.rightsHolderF Hernandez
unesp.author.orcid0000-0002-4824-9441[6]
unesp.author.orcid0000-0002-0533-3248[11]

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