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

Author(s)

Semedo, Patricia ^[1] ; Donizetti-Oliveira, Cassiano ^[1] ; Burgos-Silva, Marina ^[1] ; Cenedeze, Marco Antonio ^[1] ; Avancini Costa Malheiros, Denise Maria ^[2] ; Pacheco-Silva, Alvaro ^[1] ; Saraiva Camara, Niels Olsen ^{[3, 1]}

Affiliation

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Div Nephrol, Expt & Clin Immunol Lab, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Pathol, BR-05508900 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: LABORATORY INVESTIGATION; v. 90, n. 5, p. 685-695, MAY 2010.
• Web of Science Citations: 25

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. (AU)

• FAPESP's process: 07/07139-3 - The role of heme oxygenase 1 in different renal inflammatory process in experimental animal models
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 06/00620-5 - Mesenchymal stem cell analysis in models of acute and chronic renal ischemia
• Grantee: Patricia Semedo Kuriki
• Support Opportunities: Scholarships in Brazil - Doctorate