Please use this identifier to cite or link to this item: https://repositorio.unifesp.br/handle/11600/32485
Title: Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury
Authors: Semedo, Patricia [UNIFESP]
Donizetti-Oliveira, Cassiano [UNIFESP]
Burgos-Silva, Marina [UNIFESP]
Cenedeze, Marco Antonio [UNIFESP]
Avancini Costa Malheiros, Denise Maria
Pacheco-Silva, Alvaro [UNIFESP]
Saraiva Camara, Niels Olsen [UNIFESP]
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Keywords: mesenchymal stem cell
acute kidney injury
ischemia-reperfusion injury
fibrosis
inflammation
bone marrow
Issue Date: 1-May-2010
Publisher: Nature Publishing Group
Citation: Laboratory Investigation. New York: Nature Publishing Group, v. 90, n. 5, p. 685-695, 2010.
Abstract: 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.
URI: http://repositorio.unifesp.br/handle/11600/32485
ISSN: 0023-6837
Other Identifiers: http://dx.doi.org/10.1038/labinvest.2010.45
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