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

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

Author Semedo, Patricia Autor UNIFESP Google Scholar
Donizetti-Oliveira, Cassiano Autor UNIFESP Google Scholar
Burgos-Silva, Marina Autor UNIFESP Google Scholar
Cenedeze, Marco Antonio Autor UNIFESP Google Scholar
Avancini Costa Malheiros, Denise Maria Google Scholar
Pacheco-Silva, Alvaro Autor UNIFESP Google Scholar
Saraiva Camara, Niels Olsen Autor UNIFESP Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
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.
Keywords mesenchymal stem cell
acute kidney injury
ischemia-reperfusion injury
bone marrow
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
INCT Complex Fluids
DECIT/Ministerio da Saude
Grant number FAPESP: 06/00620-5
FAPESP: 04/08226-9
FAPESP: 07/07139-3
CNPq: 04113826-5
Date 2010-05-01
Published in Laboratory Investigation. New York: Nature Publishing Group, v. 90, n. 5, p. 685-695, 2010.
ISSN 0023-6837 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent 685-695
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000277170000004

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