Caldas Heloisa Cristina, Lojudice Fernando Henrique, Dias Cinthia, Fernandes-Charpiot Ida Maria Maximina, Baptista Maria Alice Sperto Ferreira, Kawasaki-Oyama Rosa Sayoko, Sogayar Mari Cleide, Takiya Christina Maeda, Abbud-Filho Mario
Laboratory of Immunology and Experimental Transplantation (LITEX), Department of Medicine FAMERP Medical School, Sao Jose do Rio Preto, SP, Brazil.
Department of Medicine/Nephrology-Hospital de Base, FAMERP/FUNFARME, Sao Jose do Rio Preto, SP, Brazil.
Stem Cells Int. 2017;2017:7428316. doi: 10.1155/2017/7428316. Epub 2017 Aug 3.
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- was reduced in kidneys from the BMSC group. Both types of treatments increased VEGF gene expression, TGF- 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.
诱导多能干细胞(iPS细胞)对慢性肾脏病(CKD)进展的治疗效果尚未得到证实。在本研究中,我们试图评估与骨髓间充质干细胞(BMSC)相比,iPS细胞治疗是否能延缓CKD的进展。将未治疗的5/6肾切除大鼠与接受BMSC或iPS细胞的CKD动物进行比较。研究了肾功能、组织学、免疫组织化学和基因表达。通过SRY基因表达分析追踪植入的iPS细胞。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。蛋白尿仅在iPS细胞组中减少。两种治疗均减轻了肾小球硬化,iPS细胞减少了巨噬细胞浸润,BMSC组肾脏中的转化生长因子(TGF)减少。两种治疗均增加了血管内皮生长因子(VEGF)基因表达,TGF仅在iPS细胞组中上调,白细胞介素10(IL-10)在两组中均低表达。在8只接受iPS细胞治疗的大鼠中有5只检测到SRY基因。这5只动物出现了具有组织学特征且细胞对增殖细胞核抗原(PCNA)和肾母细胞瘤蛋白抗体呈高度阳性染色的肿瘤,具有肾母细胞瘤的特征。这些结果表明,iPS细胞可能有效地延缓CKD的进展,但存在肾母细胞瘤发生的风险。