Induced Pluripotent Stem Cells Reduce Progression of Experimental Chronic Kidney Disease but Develop Wilms' Tumors.

Induced Pluripotent Stem Cells Reduce Progression of Experimental Chronic Kidney Disease but Develop Wilms' Tumors.
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DOI:
10.1155/2017/7428316
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发表时间:
2017
影响因子:
4.3
通讯作者:
Abbud-Filho M
Abbud-Filho M
中科院分区:
医学3区
文献类型:
--
作者:
Caldas HC;Lojudice FH;Dias C;Fernandes-Charpiot IMM;Baptista MASF;Kawasaki-Oyama RS;Sogayar MC;Takiya CM;Abbud-Filho M

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诱导多能干细胞(iPSs)对慢性肾病(CKD)进展的治疗作用尚未得到证实。在这项研究中,我们试图评估与骨髓间充质干细胞(BMSC)相比,iPSs治疗是否会延缓CKD的进展。将未治疗的5/6肾切除大鼠与接受BMSC或iPS的CKD动物进行比较。肾功能,组织学,免疫组化和基因表达进行了研究。通过SRY基因表达分析追踪植入的iPS。两种治疗均使血清肌酐升高最小化,显著改善清除率,并减缓疾病进展。仅iPS组尿蛋白减少。两种治疗均减少肾小球硬化,iPSs减少巨噬细胞浸润,并且来自BMSC组的肾脏中的TGF-β减少。两种类型的治疗均增加VEGF基因表达,TGF-β仅在iPS组中上调,IL-10在两组中均低表达。在用iPSs处理的5/8只大鼠中发现SRY基因。这5只动物的肿瘤具有组织学和细胞高度染色,PCNA和Wilms肿瘤蛋白抗体呈Wilms肿瘤特征。这些结果表明,iPSs可能有效地延缓CKD的进展,但具有肾母细胞瘤发展的风险。
The therapeutic effect of induced pluripotent stem cells (iPSs) on the progression of chronic kidney disease (CKD) has not yet been demonstrated. In this study, we sought to assess whether treatment with iPSs retards progression of CKD when compared with bone marrow mesenchymal stem cells (BMSCs). Untreated 5/6 nephrectomized rats were compared with CKD animals receiving BMSCs or iPSs. Renal function, histology, immunohistochemistry, and gene expression were studied. Implanted iPSs were tracked by the SRY gene expression analysis. Both treatments minimized elevation in serum creatinine, significantly improved clearance, and slowed down progression of disease. The proteinuria was reduced only in the iPS group. Both treatments reduced glomerulosclerosis, iPSs decreased macrophage infiltration, and TGF-β was reduced in kidneys from the BMSC group. Both types of treatments increased VEGF gene expression, TGF-β was upregulated only in the iPS group, and IL-10 had low expression in both groups. The SRY gene was found in 5/8 rats treated with iPSs. These 5 animals presented tumors with histology and cells highly staining positive for PCNA and Wilms' tumor protein antibody characteristics of Wilms' tumor. These results suggest that iPSs may be efficient to retard progression of CKD but carry the risk of Wilms' tumor development.
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