Bone Marrow-Derived Mesenchymal Stem Cells Repaired but Did Not Prevent Gentamicin-Induced Acute Kidney Injury through Paracrine Effects in Rats

Bone Marrow-Derived Mesenchymal Stem Cells Repaired but Did Not Prevent Gentamicin-Induced Acute Kidney Injury through Paracrine Effects in Rats

Author Reis, Luciana A. Autor UNIFESP Google Scholar
Borges, Fernanda Teixeira Autor UNIFESP Google Scholar
Simões, Manuel de Jesus Autor UNIFESP Google Scholar
Borges, Andrea Aurélio Autor UNIFESP Google Scholar
Sinigaglia-Coimbra, Rita Autor UNIFESP Google Scholar
Schor, Nestor Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract This study evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) or their conditioned medium (CM) on the repair and prevention of Acute Kidney Injury (AKI) induced by gentamicin (G). Animals received daily injections of G up to 20 days. On the 10th day, injections of BMSCs, CM, CM+trypsin, CM+RNase or exosome-like microvesicles extracted from the CM were administered. in the prevention groups, the animals received the BMSCs 24 h before or on the 5th day of G treatment. Creatinine (Cr), urea (U), FENa and cytokines were quantified. the kidneys were evaluated using hematoxylin/eosin staining and immunohystochemistry. the levels of Cr, U and FENa increased during all the periods of G treatment. the BMSC transplantation, its CM or exosome injections inhibited the increase in Cr, U, FENa, necrosis, apoptosis and also increased cell proliferation. the pro-inflammatory cytokines decreased while the anti-inflammatory cytokines increased compared to G. When the CM or its exosomes were incubated with RNase (but not trypsin), these effects were blunted. the Y chromosome was not observed in the 24-h prevention group, but it persisted in the kidney for all of the periods analyzed, suggesting that the injury is necessary for the docking and maintenance of BMSCs in the kidney. in conclusion, the BMSCs and CM minimized the G-induced renal damage through paracrine effects, most likely through the RNA carried by the exosome-like microvesicles. the use of the CM from BMSCs can be a potential therapeutic tool for this type of nephrotoxicity, allowing for the avoidance of cell transplantations.
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Financiadora de Estudos e Projetos (FINEP)
Fundacao Oswaldo Ramos (FOR)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Date 2012-09-06
Published in Plos One. San Francisco: Public Library Science, v. 7, n. 9, 11 p., 2012.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 11
Origin http://dx.doi.org/10.1371/journal.pone.0044092
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000308458400034
URI http://repositorio.unifesp.br/handle/11600/35268

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