Laboratory of Integrative and Molecular Physiology, Los Andes University, Santiago, Chile.
Clin Sci (Lond). 2013 Aug;125(4):199-210. doi: 10.1042/CS20120644.
Therapeutic approaches for CKD (chronic kidney disease) have been able to reduce proteinuria, but not diminish the disease progression. We have demonstrated beneficial effects by injection of BM (bone marrow)-derived MSCs (mesenchymal stem cells) from healthy donors in a rat model with CKD. However, it has recently been reported that BM-MSCs derived from uraemic patients failed to confer functional protection in a similar model. This suggests that autologous BM-MSCs are not suitable for the treatment of CKD. In the present study, we have explored the potential of MSCs derived from adipose tissue (AD-MSCs) as an alternative source of MSCs for the treatment of CKD. We have isolated AD-MSCs and evaluated their effect on the progression of CKD. Adult male SD (Sprague-Dawley) rats subjected to 5/6 NPX (nephrectomy) received a single intravenous infusion of 0.5×10(6) AD-MSCs or MSC culture medium alone. The therapeutic effect was evaluated by plasma creatinine measurement, structural analysis and angiogenic/epitheliogenic protein expression. AD-MSCs were detected in kidney tissues from NPX animals. This group had a significant reduction in plasma creatinine levels and a lower expression of damage markers ED-1 and α-SMA (α-smooth muscle actin) (P<0.05). In addition, treated rats exhibited a higher level of epitheliogenic [Pax-2 and BMP-7 (bone morphogenetic protein 7)] and angiogenic [VEGF (vascular endothelial growth factor)] proteins. The expression of these biomarkers of regeneration was significantly related to the improvement in renal function. Although many aspects of the cell therapy for CKD remain to be investigated, we provide evidence that AD-MSCs, a less invasive and highly available source of MSCs, exert an important therapeutic effect in this pathology.
慢性肾脏病（CKD）的治疗方法已经能够减少蛋白尿，但不能减缓疾病进展。我们在 CKD 大鼠模型中证明了来自健康供体的骨髓（BM）衍生间充质干细胞（MSCs）注射的有益效果。然而，最近有报道称，来自尿毒症患者的 BM-MSCs 在类似模型中未能发挥功能保护作用。这表明自体 BM-MSCs 不适合治疗 CKD。在本研究中，我们探索了源自脂肪组织（AD-MSCs）的 MSC 作为治疗 CKD 的 MSC 替代来源的潜力。我们分离了 AD-MSCs 并评估了它们对 CKD 进展的影响。接受 5/6 NPX（肾切除术）的成年雄性 SD（Sprague-Dawley）大鼠接受 0.5×10(6)AD-MSCs 或 MSC 培养基的单次静脉输注。通过血浆肌酐测量、结构分析和血管生成/上皮生成蛋白表达评估治疗效果。在 NPX 动物的肾脏组织中检测到 AD-MSCs。该组的血浆肌酐水平显著降低，损伤标志物 ED-1 和 α-SMA（α-平滑肌肌动蛋白）的表达降低（P<0.05）。此外，治疗组大鼠表现出更高水平的上皮生成 [Pax-2 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）] 蛋白。这些再生生物标志物的表达与肾功能的改善显著相关。尽管 CKD 的细胞治疗仍有许多方面需要研究，但我们提供的证据表明，AD-MSCs 是一种侵袭性更小、更易获得的 MSC 来源，在这种病理状态下发挥重要的治疗作用。
