Affiliation:
1. Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil
2. Nephrology Department, Federal University of São Paulo, São Paulo, Brazil
3. Immunology Department, University of São Paulo, São Paulo, Brazil
Abstract
Abstract
Progressive renal failure continues to be a challenge. The use of bone marrow cells represents a means of meeting that challenge. We used lineage-negative (Lin−) cells to test the hypothesis that Lin− cell treatment decreases renal injury. Syngeneic Fischer 344 rats were divided into four groups: sham (laparotomy only, untreated); Nx (five-sixth nephrectomy and untreated); NxLC1 (five-sixth nephrectomy and receiving 2 × 106 Lin− cells on postnephrectomy day 15); and NxLC3 (five-sixth nephrectomy and receiving 2 × 106 Lin− cells on postnephrectomy days 15, 30, and 45). On postoperative day 16, renal mRNA expression of interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 was lower in NxLC rats than in Nx rats. On postnephrectomy day 60, NxLC rats presented less proteinuria, glomerulosclerosis, anemia, renal infiltration of immune cells, and protein expression of monocyte chemoattractant protein-1, as well as decreased interstitial area. Immunostaining for proliferating cell nuclear antigen showed that, in comparison with sham rats, Nx rats presented greater cell proliferation, whereas NxLC1 rats and NxLC3 rats presented less cell proliferation than did Nx rats. Protein expression of the cyclin-dependent kinase inhibitor p21 and of vascular endothelial growth factor increased after nephrectomy and decreased after Lin− cell treatment. On postnephrectomy day 120, renal function (inulin clearance) was significantly better in Lin− cell-treated rats than in untreated rats. Lin− cell treatment significantly improved survival. These data suggest that Lin− cell treatment protects against chronic renal failure.
Funder
Fundação de Amparo à Pesquisa do Estado de São Paulo
FAPESP [Foundation for the Support of Research in the State of São Paulo]
Laboratórios de Investigação Médica (Medical Investigation Laboratories) of the Faculdade de Medicina da Universidade de São Paulo (University of Sao Paulo School of Medicine) Hospital das Clínicas
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq [National Council for Scientific and Technological Development]
FAPESP
CNPq and FAPESP
Publisher
Oxford University Press (OUP)
Subject
Cell Biology,Developmental Biology,Molecular Medicine
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