Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury

Detalhes bibliográficos
Autor(a) principal: Semedo, Patricia [UNIFESP]
Data de Publicação: 2010
Outros Autores: Donizetti-Oliveira, Cassiano [UNIFESP], Burgos-Silva, Marina [UNIFESP], Cenedeze, Marco Antonio [UNIFESP], Malheiros, Denise Maria Avancini Costa, Pacheco-Silva, Alvaro [UNIFESP], Camara, Niels Olsen Saraiva [UNIFESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: https://dx.doi.org/10.1038/labinvest.2010.45
https://repositorio.unifesp.br/handle/11600/32485
Resumo: One of the early phases that lead to fibrosis progression is inflammation. Once this stage is resolved, fibrosis might be prevented. Bone marrow mononuclear cells (BMMCs) are emerging as a new therapy for several pathologies, including autoimmune diseases, because they enact immunosuppression. in this study we aimed to evaluate the role of BMMC administration in a model of kidney fibrosis induced by an acute injury. C57Bl6 mice were subjected to unilateral severe ischemia by clamping the left renal pedicle for 1 h. BMMCs were isolated from femurs and tibia, and after 6 h of reperfusion, 1 x 10(6) cells were administrated intraperitoneally. At 24 h after surgery, treated animals showed a significant decrease in creatinine and urea levels when compared with untreated animals. Different administration routes were tested. Moreover, interferon (IFN) receptor knockout BMMCs were used, as this receptor is necessary for BMMC activation. Labeled BMMCs were found in ischemic kidney on FACS analysis. This improved outcome was associated with modulation of inflammation in the kidney and systemic modulation, as determined by cytokine expression profiling. Despite non-amelioration of functional parameters, kidney mRNA expression of interleukin (IL)-6 at 6 weeks was lower in BMMC-treated animals, as were levels of collagen 1, connective tissue growth factor (CTGF), transforming growth factor-beta (TGF-beta) and vimentin. Protective molecules, such as IL-10, heme oxygenase 1 (HO-1) and bone morphogenetic 7 (BMP-7), were increased in treated animals after 6 weeks. Moreover, Masson and Picrosirius red staining analyses showed less fibrotic areas in the kidneys of treated animals. Thus, early modulation of inflammation by BMMCs after an ischemic injury leads to reduced fibrosis through modulation of early inflammation.
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spelling Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injuryMesenchymal stem cellAcute kidney injuryIschemia-reperfusion injuryFibrosisInflammationBone marrowOne of the early phases that lead to fibrosis progression is inflammation. Once this stage is resolved, fibrosis might be prevented. Bone marrow mononuclear cells (BMMCs) are emerging as a new therapy for several pathologies, including autoimmune diseases, because they enact immunosuppression. in this study we aimed to evaluate the role of BMMC administration in a model of kidney fibrosis induced by an acute injury. C57Bl6 mice were subjected to unilateral severe ischemia by clamping the left renal pedicle for 1 h. BMMCs were isolated from femurs and tibia, and after 6 h of reperfusion, 1 x 10(6) cells were administrated intraperitoneally. At 24 h after surgery, treated animals showed a significant decrease in creatinine and urea levels when compared with untreated animals. Different administration routes were tested. Moreover, interferon (IFN) receptor knockout BMMCs were used, as this receptor is necessary for BMMC activation. Labeled BMMCs were found in ischemic kidney on FACS analysis. This improved outcome was associated with modulation of inflammation in the kidney and systemic modulation, as determined by cytokine expression profiling. Despite non-amelioration of functional parameters, kidney mRNA expression of interleukin (IL)-6 at 6 weeks was lower in BMMC-treated animals, as were levels of collagen 1, connective tissue growth factor (CTGF), transforming growth factor-beta (TGF-beta) and vimentin. Protective molecules, such as IL-10, heme oxygenase 1 (HO-1) and bone morphogenetic 7 (BMP-7), were increased in treated animals after 6 weeks. Moreover, Masson and Picrosirius red staining analyses showed less fibrotic areas in the kidneys of treated animals. Thus, early modulation of inflammation by BMMCs after an ischemic injury leads to reduced fibrosis through modulation of early inflammation.Univ São Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Div Nephrol, Expt & Clin Immunol Lab, São Paulo, BrazilUniv São Paulo, Dept Pathol, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Div Nephrol, Expt & Clin Immunol Lab, São Paulo, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)INCT Complex FluidsDECIT/Ministério da SaúdeFAPESP: 06/00620-5FAPESP: 04/08226-9FAPESP: 07/07139-3CNPq: 04113826-5Nature Publishing GroupUniversidade de São Paulo (USP)Universidade Federal de São Paulo (UNIFESP)Semedo, Patricia [UNIFESP]Donizetti-Oliveira, Cassiano [UNIFESP]Burgos-Silva, Marina [UNIFESP]Cenedeze, Marco Antonio [UNIFESP]Malheiros, Denise Maria Avancini CostaPacheco-Silva, Alvaro [UNIFESP]Camara, Niels Olsen Saraiva [UNIFESP]2016-01-24T13:59:36Z2016-01-24T13:59:36Z2010-05-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion685-695https://dx.doi.org/10.1038/labinvest.2010.45Laboratory Investigation. New York: Nature Publishing Group, v. 90, n. 5, p. 685-695, 2010.10.1038/labinvest.2010.450023-6837https://repositorio.unifesp.br/handle/11600/32485WOS:000277170000004engLaboratory Investigationinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2022-07-20T19:20:52Zoai:repositorio.unifesp.br/:11600/32485Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652022-07-20T19:20:52Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury
title Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury
spellingShingle Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury
Semedo, Patricia [UNIFESP]
Mesenchymal stem cell
Acute kidney injury
Ischemia-reperfusion injury
Fibrosis
Inflammation
Bone marrow
title_short Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury
title_full Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury
title_fullStr Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury
title_full_unstemmed Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury
title_sort Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury
author Semedo, Patricia [UNIFESP]
author_facet Semedo, Patricia [UNIFESP]
Donizetti-Oliveira, Cassiano [UNIFESP]
Burgos-Silva, Marina [UNIFESP]
Cenedeze, Marco Antonio [UNIFESP]
Malheiros, Denise Maria Avancini Costa
Pacheco-Silva, Alvaro [UNIFESP]
Camara, Niels Olsen Saraiva [UNIFESP]
author_role author
author2 Donizetti-Oliveira, Cassiano [UNIFESP]
Burgos-Silva, Marina [UNIFESP]
Cenedeze, Marco Antonio [UNIFESP]
Malheiros, Denise Maria Avancini Costa
Pacheco-Silva, Alvaro [UNIFESP]
Camara, Niels Olsen Saraiva [UNIFESP]
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Semedo, Patricia [UNIFESP]
Donizetti-Oliveira, Cassiano [UNIFESP]
Burgos-Silva, Marina [UNIFESP]
Cenedeze, Marco Antonio [UNIFESP]
Malheiros, Denise Maria Avancini Costa
Pacheco-Silva, Alvaro [UNIFESP]
Camara, Niels Olsen Saraiva [UNIFESP]
dc.subject.por.fl_str_mv Mesenchymal stem cell
Acute kidney injury
Ischemia-reperfusion injury
Fibrosis
Inflammation
Bone marrow
topic Mesenchymal stem cell
Acute kidney injury
Ischemia-reperfusion injury
Fibrosis
Inflammation
Bone marrow
description One of the early phases that lead to fibrosis progression is inflammation. Once this stage is resolved, fibrosis might be prevented. Bone marrow mononuclear cells (BMMCs) are emerging as a new therapy for several pathologies, including autoimmune diseases, because they enact immunosuppression. in this study we aimed to evaluate the role of BMMC administration in a model of kidney fibrosis induced by an acute injury. C57Bl6 mice were subjected to unilateral severe ischemia by clamping the left renal pedicle for 1 h. BMMCs were isolated from femurs and tibia, and after 6 h of reperfusion, 1 x 10(6) cells were administrated intraperitoneally. At 24 h after surgery, treated animals showed a significant decrease in creatinine and urea levels when compared with untreated animals. Different administration routes were tested. Moreover, interferon (IFN) receptor knockout BMMCs were used, as this receptor is necessary for BMMC activation. Labeled BMMCs were found in ischemic kidney on FACS analysis. This improved outcome was associated with modulation of inflammation in the kidney and systemic modulation, as determined by cytokine expression profiling. Despite non-amelioration of functional parameters, kidney mRNA expression of interleukin (IL)-6 at 6 weeks was lower in BMMC-treated animals, as were levels of collagen 1, connective tissue growth factor (CTGF), transforming growth factor-beta (TGF-beta) and vimentin. Protective molecules, such as IL-10, heme oxygenase 1 (HO-1) and bone morphogenetic 7 (BMP-7), were increased in treated animals after 6 weeks. Moreover, Masson and Picrosirius red staining analyses showed less fibrotic areas in the kidneys of treated animals. Thus, early modulation of inflammation by BMMCs after an ischemic injury leads to reduced fibrosis through modulation of early inflammation.
publishDate 2010
dc.date.none.fl_str_mv 2010-05-01
2016-01-24T13:59:36Z
2016-01-24T13:59:36Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://dx.doi.org/10.1038/labinvest.2010.45
Laboratory Investigation. New York: Nature Publishing Group, v. 90, n. 5, p. 685-695, 2010.
10.1038/labinvest.2010.45
0023-6837
https://repositorio.unifesp.br/handle/11600/32485
WOS:000277170000004
url https://dx.doi.org/10.1038/labinvest.2010.45
https://repositorio.unifesp.br/handle/11600/32485
identifier_str_mv Laboratory Investigation. New York: Nature Publishing Group, v. 90, n. 5, p. 685-695, 2010.
10.1038/labinvest.2010.45
0023-6837
WOS:000277170000004
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Laboratory Investigation
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 685-695
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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