A model for ex vivo renal angiogenesis

被引:9
作者
Brodsky, SV
Smith, M
Kashgarian, M
Goligorsky, MS
机构
[1] New York Med Coll, Dept Med, Renal Res Inst, BSB, Valhalla, NY 10595 USA
[2] SUNY Stony Brook, Dept Med, Div Cardiol, Stony Brook, NY 11794 USA
[3] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA
来源
NEPHRON EXPERIMENTAL NEPHROLOGY | 2003年 / 93卷 / 01期
关键词
angiogenesis; kidney explants; diabetes mellitus;
D O I
10.1159/000066653
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Attempts to study renal angiogenesis have been hampered by the lack of an appropriate model. Here we present data on a successful ex vivo culture of renal medullary explants in three-dimensional collagen 1 or Matrigel lattices and characterize the dynamics of capillary formation by sprouting endothelial cells. Initially, endothelial cells represented 71+/-3% among the sprouting cells, but within a week growing capillaries were comprised exclusively of endothelial cells. The quantitative analysis showed that the number of sprouting capillaries progressively increased until 12 days in culture, after which capillaries underwent involution. Occasional formation of glomeruloid bodies was noted. Capillaries were characterized by a well-defined lumen, whereas glomeruloid bodies showed cellular debris occupying the luminal space. In view of the existing controversy regarding angiogenic competence in diabetic nephropathy, we applied this ex vivo culture system to Zucker diabetic rat model of diabetes mellitus. Comparative analysis of capillary sprouting in Zucker diabetic fat and lean nondiabetic control rats showed no differences in angiogenic properties of renal explants obtained at the age of 11 weeks. However, when kidneys were obtained from rats at age of 21 weeks, the capillary sprouting was significantly reduced in Zucker diabetic rats compared to age-matched lean rats. The rate of capillary involution was unaffected in Zucker diabetic rats. In conclusion, the data presented herein delineate the first successful ex vivo model of angiogenesis initiated from the renal medullary explants of adult rats and provide evidence of impaired angiogenesis in Zucker diabetic rats with the established, but not with incipient diabetes mellitus. Copyright (C) 2003 S. Karger AG, Basel.
引用
收藏
页码:E46 / E52
页数:7
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