The renoprotective effect of bone marrow-derived endothelial progenitor cell transplantation on acute ischemia-reperfusion injury in rats.

OBJECTIVE: To investigate the renoprotective effects of exogenous endothelial progenitor cells (EPCs) on acute renal ischemia-reperfusion (I/R) injury in rats. METHODS: EPCs were collected by in vitro culture of mononuclear cells derived from rat bone marrow. The EPC labeling was performed using chloromethyl-benzamidodialkylcarbocyanine (CM-Dil). Sprague-Dawley rats were equally randomized into an I/R, an EPC, and a control group. We evaluated blood urea nitrogen (BUN) and serum creatinine (Scr), kidney morphology, apoptosis and microvessel density. EPC homing into I/R injured kidneys was observed using a fluorescence microscope. RESULTS: After EPC transplantation, CM-Dil-labeled EPCs were noted at the corticomedullary junction of injured kidneys. The levels of BUN and Scr were markedly lower among the EPC than the I/R group (P < .05). The histopathologic score was higher in the I/R than the EPC group (P < .05). Apoptosis of tubular epithelial cells was substantially reduced among EPC-treated rats (P < .01). In addition, more CD34(+) microvessels were documented among the EPC than the other two groups (P < .01). The expression levels of vascular endothelial growth factor (VEGF) were also increased greatly in the EPC group (P < .05). CONCLUSION: Transplanted exogenous EPCs exert protective effects on renal function by maintaining the integrity of peritubular capillaries after I/R injury.

Effects of ischemic preconditioning in the late phase on homing of endothelial progenitor cells in renal ischemia/reperfusion injury.

OBJECTIVE: The aim of this study was to determine whether the mobilization and recruitment of endothelial progenitor cells (EPCs) contribute to the protection of kidneys from ischemia/reperfusion (I/R) injury after ischemic preconditioning (IPC) during the late phase. METHODS: Seventy-five male Sprague-Dawley rats were divided into the following groups: sham-operated (group A; n = 25), ischemia/reperfusion hosts that underwent 45 minutes of left renal artery ischemia (group B; n = 25), and ischemic preconditioning-treated group (group C; n = 25). Group C underwent 3 cycles of 5 minutes of occlusion and 5 minutes of reperfusion followed by 24 hours of reperfusion before the following 45 minutes of occlusion. Serum samples were collected and renal tissues harvested for histological examination terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemical staining, and Western blot analysis to determine the expression levels of CD34, VEGFR-2 (Vascular Endothelial Growth Factor Receptor 2)/flk-1, vascular endothelial growth factor (VEGF), and stromal cell-derived factor-1α (SDF-1α). RESULTS: Compared with group B, the levels of blood urea nitrogen (BUN), serum creatinine (Scr) and acute tubulointerstitial injury at 24 hours after operation were significantly reduced in group C. At 72 hours, tubular epithelial cell apoptosis was also decreased (17.6 ± 4.45 vs 63.8 ± 6.10; P < .01). CD34+ and flk-1+ cells that mostly accumulated in the medullopapillary parenchyma were significantly increased at 72 hours (P < .05). Expression levels of VEGF and SDF-1α were also significantly higher in group C (P < .05). CONCLUSION: The present work suggested that IPC protected kidneys from IR injury in the later phase through enhanced mobilization and recruitment of EPCs. VEGF and SDF-1α may play important roles in this protective effect.