Intrarenal injection of bone marrow-derived angiogenic cells reduces endothelial injury and mesangial cell activation in experimental glomerulonephritis
Intrarenal injection of bone marrow-derived angiogenic cells reduces endothelial injury and mesangial cell activation in experimental glomerulonephritis
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DOI：
10.1681/asn.2004050367
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发表时间：
2005-04-01
影响因子：
13.6
通讯作者：
Fujita, T
中科院分区：
文献类型：
--
作者：
Uchimura, H;Marumo, T;Fujita, T
肾小球内皮细胞的丧失被认为是肾小球损伤进展的原因。尽管在内皮损伤的疾病模型中观察到了通过给予骨髓来源的内皮祖细胞诱导的治疗性血管生成，但对肾脏疾病的影响尚未阐明。本研究旨在探讨经培养修饰的骨髓单个核细胞是否能减轻抗Thy1.1肾炎患者的肾小球内皮损伤。在促进内皮祖细胞生长的条件下培养后，将骨髓单核细胞用荧光标记物CM-DiI标记，并注射到患有抗Thy 1.1肾小球肾炎的刘易斯大鼠的左肾动脉中。与接受细胞输注的肾炎大鼠的右肾相比，左肾肾小球内皮细胞的减少显著减弱。左肾肾小球损伤评分、系膜α-平滑肌肌动蛋白阳性面积和巨噬细胞浸润显著减少。CM-DiI阳性细胞分布于左肾的肾小球中，但不分布于右肾的肾小球中。在CM-DiI标记的肾小球细胞中，16.5 +/- 1.2%的细胞被内皮标记物大鼠内皮细胞抗原-1染色。培养修饰的单核细胞分泌281.2 +/- 85.0 pg的血管内皮生长因子/105个细胞/天。总之，动脉内给予培养修饰的骨髓单个核细胞可减少抗Thy1.1肾小球肾炎的内皮损伤和系膜激活。整合到肾小球内皮衬里和生产的血管生成因子（S）可能有助于培养修饰的单核细胞对肾小球损伤的保护作用。
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 a-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 105 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.