Immunosuppressive and remodelling properties of mesenchymal stem cells in a model of chronic kidney disease

Author(s)

Semedo, Patricia ; Correa-Costa, Matheus ; Cenedeze, Marcos Antonio ; Avancini Costa Malheiros, Denise Maria ; Massola Shimizu, Maria Heloisa ; Seguro, Antonio Carlos ; Pacheco-Silva, Alvaro ; Saraiva Camara, Niels Olsen

• Document type: Journal article
• Source: Einstein (São Paulo); v. 7, n. 4, p. 11-pg., 2009-10-01.

Abstract

Objective: To investigate the role of mesenchymal stem cells in fibrogenesis using a model of chronic renal insufficiency. Methods: Mesenchymal stem cells were obtained from tibias and femurs of Wistar-EPM rats. After three to five passages, the cells were submitted to phenotypic analyses and differentiation. Wistar rats were submitted to the 5/6 nephrectomy model, and 2.10(5) mesenchymal stem cells were administered intravenously to each rat every two weeks until the eighth week. Results: Sex-determining region Y was observed in female rats treated with stem cells. Serum and urine analyses showed improvement of functional parameters in mesenchymal stem cells treated animals, such as creatinine, serum urea, and proteinuria. Moreover, hemocrit analysis showed improvement of anemia in mesenchymal stem cells treated animals. Masson's Trichromium and Picrosirius Red staining demonstrated reduced levels of fibrosis in mesenchymal stem cells treated in animals. These results were corroborated by reduced vimentin, collagen I, TGF beta, FSP-1, MCP-1 and Smad3 mRNA expression. Renal IL-6 and TNF alpha mRNA expression levels were significantly decreased after mesenchymal stem cells treatment, while IL-4 and IL-10 expression were increased. Serum expression of IL-1 alpha, IL-1 beta, IL-6, IFN-gamma, TNF-alpha, and IL-10 was decreased in mesenchymal cell-treated animals. Conclusions: Altogether, these results suggest that mesenchymal stem cells therapy can indeed modulate the inflammatory response that follows the initial phase of a chronic renal lesion. The immunosuppresive and remodeling properties of the mesenchymal stem cells may be involved in the improved fibrotic outcome. (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