Biomaterial seeded with bone marrow cells in experimental chronic renal failure: effect on disease progression in two different stages

• Grant number: 10/08912-0
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2011
• End date: December 31, 2012
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Mario Abbud Filho
• Grantee: Mario Abbud Filho
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil
• Associated researchers: Domingo Marcolino Braile ; Eny Maria Goloni Bertollo ; Heloisa Cristina Caldas

Abstract

Stem cell therapy (CT), in which there is the potential for treatment of chronic diseases, may be a promising strategy to repair and/or slow the progression of CRF. There are questions concerning cell type, the quantity of cells necessary, the best method of administration, and the ideal location for deployment of CT, and the role these cells play in the repair of renal tissue. In addition, there is evidence that biomaterials (BM) cause inflammation and modify the immune response, as well as having potential for tissue remodeling. That is why our primary objective was to evaluate the combined effects of CT and BM in the progression of CRF and to study the effects of this therapy at different stages of the disease. In this project, we will: 1)- investigate the role of fibrogenic, angiogenic, and cytokine factors on the pathophysiological mechanisms involved in the stabilization and/or slowing of the progression of CRF observed in a previous study; 2)- analyze the migration of cells implanted in BM by the presence of the SRY gene in female animals that received cell therapy and further investigate the role of stem cells in cellular and inflammatory mechanisms possibly involved in CRF. Seventy-five rats were divided into 14 groups according to: 1)- the amount of renal parenchyma injured (5/6 or 2/3); 2)- use of BM as a framework for cellular implantation, 3)- the type of CT employing mononuclear cells or mesenchymal (MSC) CT, and the use of BM. The evaluation of renal function will be performed at baseline, and after 45 and 90 days of cell therapy. Additionally, the expression of VEGF genes, collagen I, TNF-±, IL-6, TGF-², and IL-10 will be quantified in renal tissue. The study will follow the migration of the cells implanted at the location of SRY by PCR. The immunohistochemical study will be conducted to evaluate the number of macrophages, myofibroblasts, TGF-², angiotensin II, endothelin, fibronectin, and PCNA (AU)