title: Intrarenal injection of bone marrow-derived angiogenic cells reduces endothelial injury and mesangial cell activation in experimental glomerulonephritis.
abstract: Loss of glomerular endothelial cells has been suggested to contribute to the progression of glomerular injury. Although therapeutic angiogenesis induced by administration of bone marrow-derived endothelial progenitor cells has been observed in disease models of endothelial injury, the effects on renal disease have not been clarified. Whether administration of culture-modified bone marrow mononuclear cells would mitigate the glomerular endothelial injury in anti-Thy1.1 nephritis was investigated. After cultivation under conditions that promote endothelial progenitor cell growth, bone marrow mononuclear cells were labeled with CM-DiI, a fluorescence marker, and injected into the left renal artery of Lewis rats with anti-Thy1.1 glomerulonephritis. The decrease in glomerular endothelial cells was significantly attenuated in the left kidney, as compared with the right, in nephritic rats that received the cell infusion. Glomerular injury score, the area positive for mesangial alpha-smooth muscle actin, and infiltration of macrophages were significantly decreased in the left kidney. CM-DiI-positive cells were distributed in glomeruli of the left kidney but not in those of the right kidney. Among CM-DiI-labeled cells incorporated into glomeruli, 16.5 +/- 1.2% of cells were stained with an endothelial marker, rat endothelial cell antigen-1. Culture-modified mononuclear cells secreted 281.2 +/- 85.0 pg of vascular endothelial growth factor per 10(5) cells per day. In conclusion, intra-arterial administration of culture-modified bone marrow mononuclear cells reduced endothelial injury and mesangial activation in anti-Thy1.1 glomerulonephritis. Incorporation into the glomerular endothelial lining and production of angiogenic factor(s) are likely to contribute to the protective effects of culture-modified mononuclear cells against glomerular injury.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Uchimura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Marumo
authors.forename: Osamu
authors.initials: O
authors.lastname: Takase
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Fujio
authors.initials: F
authors.lastname: Shimizu
authors.forename: Matsuhiko
authors.initials: M
authors.lastname: Hayashi
authors.forename: Takao
authors.initials: T
authors.lastname: Saruta
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hishikawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods*; D003404:Creatinine / Q000097:blood; D004730:Endothelium, Vascular / Q000473:pathology*; D005920:Glomerular Mesangium / Q000473:pathology / Q000503:physiopathology*; D005921:Glomerulonephritis / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy* / Q000652:urine; D007269:Injections, Intra-Arterial; D008297:Male; D018919:Neovascularization, Physiologic; D009994:Osmolar Concentration; D011507:Proteinuria / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D012077:Renal Artery; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D000954:Antigens, Surface; D042461:Vascular Endothelial Growth Factor A; D003404:Creatinine