Bone marrow-derived endothelial progenitor cells confer renal protection in a murine chronic renal failure model.
Bone marrow-derived endothelial progenitor cells confer renal protection in a murine chronic renal failure model.
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DOI：
10.1152/ajprenal.00019.2010
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发表时间：
2010-08
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通讯作者：
Odongua Sangidorj;S. Yang;H. Jang;J. P. Lee;R. Cha;S. M. Kim;C. Lim;Y. S. Kim
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作者：
Odongua Sangidorj;S. Yang;H. Jang;J. P. Lee;R. Cha;S. M. Kim;C. Lim;Y. S. Kim
内皮细胞损伤和血管生成受损是导致慢性肾功能衰竭（CRF）的主要原因。内皮祖细胞（EPC）治疗对CRF进展的影响尚未确定。我们对C57BL/6小鼠行5/6肾切除术以诱导CRF。从骨髓中分离EPCs，在条件培养基中培养，用表面标记分析对其进行表征。观察CRF小鼠和epc处理的CRF （EPC-CRF）小鼠肾脏功能和组织学特征的一系列变化。过继性转移的内皮祖细胞存在于肾小球和小管间质区域，直到转移后第8周。在CRF小鼠中，肾功能随着时间的推移而稳步恶化，而EPC-CRF组肾功能恶化较小，蛋白尿减少，肾脏结构相对保存。在疾病早期，EPC-CRF组的肾脏促炎细胞因子和粘附分子的表达已经下降，此时CRF和EPC-CRF小鼠的肾功能和组织学没有差异。血管生成分子包括VEGF、KDR和血小板反应蛋白-1，在CRF组降低，通过EPC治疗恢复。综上所述，EPCs输注到损伤的肾脏中可以保护肾脏免受炎症的影响，从而使肾脏的功能和结构得以保存。我们的研究表明EPCs是一种潜在的治疗CRF的新方法。
Endothelial cell damage and impaired angiogenesis substantially contribute to the progression of chronic renal failure (CRF). The effect of endothelial progenitor cell (EPC) treatment on the progression of CRF is yet to be determined. We performed 5/6 nephrectomy to induce CRF in C57BL/6 mice. EPCs were isolated from bone marrow, grown in conditioned medium, and characterized with surface marker analysis. The serial changes in kidney function and histological features were scrutinized in CRF mice and EPC-treated CRF (EPC-CRF) mice. Adoptively transferred EPCs were present at the glomeruli and the tubulointerstitial area until week 8 after transfer. In CRF mice, renal function deteriorated steadily over time, whereas the EPC-CRF group showed less deterioration of renal function as well as reduced proteinuria along with a relatively preserved kidney structure. Renal expression of proinflammatory cytokines and adhesion molecules was already decreased in the EPC-CRF group at the early stage of disease, at which point the renal function and histology of CRF and EPC-CRF mice were not different. Angiogenic molecules including VEGF, KDR, and thrombospondin-1, which were decreased in the CRF group, were restored by EPC treatment. In conclusion, EPCs trafficked into the injured kidney protected the kidney from the inflammatory condition and consequently resulted in functional and structural renal preservation. Our study suggests EPCs as a potential candidate for a novel therapeutic approach in CRF.