Mesenchymal Stem Cells Protective Effect in Adriamycin Model of Nephropathy
Mesenchymal Stem Cells Protective Effect in Adriamycin Model of Nephropathy
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DOI：
10.3727/096368908787236567
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Ghiggeri, Gian Marco
中科院分区：
文献类型：
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作者：
Magnasco, Alberto;Corselli, Mirko;Ghiggeri, Gian Marco
间充质干细胞（MSCs）可能在肾组织损伤后的再生中具有价值；然而，缺乏生物学知识和动物模型结果的可变性限制了它们的利用。我们利用阿霉素（ADR）作为肾毒性模型，在体外和体内研究了间充质干细胞对足细胞的影响。采用体内实验方法，对雄性Sprague-Dawley大鼠（共60只）采用不同ADR方案诱导急性和慢性肾病。a)不良反应同时给予MSCs， b)在不良反应发生60天后给予主动脉，c)在不良反应发生后给予尾静脉。用PKH26-MSCs评估归巢性。MSCs对ADR诱导足细胞凋亡的体外修复作用。当MSCs/足细胞共培养比例为1:1时，72h的效果最大（挽救80%）。MSCs没有改变临床参数（即蛋白尿、血清肌酐、血脂），但在不良反应同时给予时，可以保护肾脏免受严重肾小球硬化的影响。不良反应后60天给予间充质干细胞的大鼠出现同样严重的肾损害。注射后1 ~ 24 h，肾小管间质区仅检出少量MSCs，肾小球未检出MSCs。MSCs在体外减少ADR处理足细胞的凋亡。早期和反复输注MSCs可减弱慢性adr肾病的肾小球损伤。MSCs没有改变蛋白尿和进展为肾衰竭，这意味着在该模型中缺乏再生潜力。
Mesenchymal stem cells (MSCs) may be of value in regeneration of renal tissue after damage; however, lack of biological knowledge and variability of results in animal models limit their utilization. We studied the effects of MSCs on podocytes in vitro and in vivo utilizing adriamycin (ADR) as a model of renal toxicity. The in vivo experimental approach was carried out in male Sprague-Dawley rats (overall 60 animals) treated with different ADR schemes to induce acute and chronic nephrosis. MSCs were given a) concomitantly to ADR in tail vein or b) in aorta and c) in tail vein 60 days after ADR. Homing was assessed with PKH26-MSCs. MSCs rescued podocytes from apoptosis induced by ADR in vitro. The maximal effect (80% rescue) was obtained with MSCs/podocytes coculture ratio of 1:1 for 72 h. All rats treated with ADR developed nephrosis. MSCs did not modify the clinical parameters (i.e., proteinuria, serum creatinine, lipids) but protected the kidney from severe glomerulosclerosis when given concomitantly to ADR. Rats given MSCs 60 days after ADR developed the same severe renal damage. Only a few MSCs were found in renal tubule-interstitial areas 1-24 h after injection and no MSCs were detected in glomeruli. MSCs reduced apoptosis of podocytes treated with ADR in vitro. Early and repeated MSCs infusion blunted glomerular damage in chronic ADR-induced nephropathy. MSCs did not modify proteinuria and progression to renal failure, which implies lack of regenerative potential in this model.