Laboratory of Integrative and Molecular Physiology, Los Andes University, Santiago, Chile.
Clin Sci (Lond). 2011 Dec;121(11):489-99. doi: 10.1042/CS20110108.
CKD (chronic kidney disease) has become a public health problem. The therapeutic approaches have been able to reduce proteinuria, but have not been successful in limiting disease progression. In this setting, cell therapies associated with regenerative effects are attracting increasing interest. We evaluated the effect of MSC (mesenchymal stem cells) on the progression of CKD and the expression of molecular biomarkers associated with regenerative effects. Adult male Sprague-Dawley rats subjected to 5/6 NPX (nephrectomy) received a single intravenous infusion of 0.5×106 MSC or culture medium. A sham group subjected to the same injection was used as the control. Rats were killed 5 weeks after MSC infusion. Dye tracking of MSC was followed by immunofluorescence analysis. Kidney function was evaluated using plasma creatinine. Structural damage was evaluated by H&E (haematoxylin and eosin) staining, ED-1 abundance (macrophages) and interstitial α-SMA (α-smooth muscle actin). Repairing processes were evaluated by functional and structural analyses and angiogenic/epitheliogenic protein expression. MSC could be detected in kidney tissues from NPX animals treated with intravenous cell infusion. This group presented a marked reduction in plasma creatinine levels and damage markers ED-1 and α-SMA (P<0.05). In addition, treated rats exhibited a significant induction in epitheliogenic [Pax-2, bFGF (basic fibroblast growth factor) and BMP-7 (bone morphogenetic protein-7)] and angiogenic [VEGF (vascular endothelial growth factor) and Tie-2] proteins. The expression of these biomarkers of regeneration was significantly related to the increase in renal function. Many aspects of the cell therapy in CKD remain to be investigated in more detail: for example, its safety, low cost and the possible need for repeated cell injections over time. Beyond the undeniable importance of these issues, what still needs to be clarified is whether MSC administration has a real effect on the treatment of this pathology. It is precisely to this point that the present study aims to contribute.
慢性肾脏病（CKD）已成为一个公共卫生问题。治疗方法已经能够减少蛋白尿，但未能成功地限制疾病进展。在这种情况下，与再生作用相关的细胞疗法引起了越来越多的关注。我们评估了 MSC（间充质干细胞）对 CKD 进展和与再生作用相关的分子生物标志物表达的影响。接受 5/6 NPX（肾切除术）的成年雄性 Sprague-Dawley 大鼠接受单次静脉输注 0.5×106 MSC 或培养基。接受相同注射的假手术组用作对照。MSC 输注后 5 周处死大鼠。通过免疫荧光分析跟踪 MSC 的示踪染料。使用血浆肌酐评估肾功能。通过 H&E（苏木精和伊红）染色、ED-1 丰度（巨噬细胞）和间质 α-SMA（α-平滑肌肌动蛋白）评估结构损伤。通过功能和结构分析以及血管生成/上皮生成蛋白表达评估修复过程。在接受静脉细胞输注的 NPX 动物的肾脏组织中可以检测到 MSC。该组的血浆肌酐水平和损伤标志物 ED-1 和 α-SMA 明显降低（P<0.05）。此外，治疗大鼠显著诱导上皮生成[Pax-2、bFGF（碱性成纤维细胞生长因子）和 BMP-7（骨形态发生蛋白-7）]和血管生成[VEGF（血管内皮生长因子）和 Tie-2]蛋白。这些再生生物标志物的表达与肾功能的增加显著相关。在 CKD 中，细胞治疗的许多方面仍需要更详细地研究：例如，其安全性、低成本和可能需要随着时间的推移重复细胞注射。除了这些问题的不可否认的重要性之外，仍需要澄清的是 MSC 给药是否对这种病理的治疗有实际影响。正是为了这一点，本研究旨在做出贡献。
