Lineage-negative bone marrow cells protect against chronic renal failure.
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 x 10(6) Lin(-) cells on postnephrectomy day 15); and NxLC3 (five-sixth nephrectomy and receiving 2 x 10(6) Lin(-) cells on postnephrectomy days 15, 30, and 45). On postoperative day 16, renal mRNA expression of interleukin (IL)-1beta, tumor necrosis factor-alpha, 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.
Alexandre
Cristianne Silva
CS
Nephrology Department, University of São Paulo School of Medicine, Brazil.
Volpini
Rildo Aparecido
RA
Shimizu
Maria Heloísa
MH
Sanches
Talita Rojas
TR
Semedo
Patricia
P
di Jura
Vera Lúcia
VL
Câmara
Niels Olsen
NO
Seguro
Antonio Carlos
AC
Andrade
Lúcia
L
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D016130:Immunophenotyping; D019012:Integrin beta1 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D009392:Nephrectomy; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D019718:Receptors, CXCR4 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018800:Thy-1 Antigens / Q000378:metabolism
D018952:Antigens, CD34; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D018960:Hyaluronan Receptors; D019012:Integrin beta1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019718:Receptors, CXCR4; D018800:Thy-1 Antigens; D017493:Leukocyte Common Antigens