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

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). U...

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Main Authors: Heloisa Cristina Caldas, Fernando Henrique Lojudice, Cinthia Dias, Ida Maria Maximina Fernandes-Charpiot, Maria Alice Sperto Ferreira Baptista, Rosa Sayoko Kawasaki-Oyama, Mari Cleide Sogayar, Christina Maeda Takiya, Mario Abbud-Filho
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2017/7428316
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author Heloisa Cristina Caldas
Fernando Henrique Lojudice
Cinthia Dias
Ida Maria Maximina Fernandes-Charpiot
Maria Alice Sperto Ferreira Baptista
Rosa Sayoko Kawasaki-Oyama
Mari Cleide Sogayar
Christina Maeda Takiya
Mario Abbud-Filho
author_facet Heloisa Cristina Caldas
Fernando Henrique Lojudice
Cinthia Dias
Ida Maria Maximina Fernandes-Charpiot
Maria Alice Sperto Ferreira Baptista
Rosa Sayoko Kawasaki-Oyama
Mari Cleide Sogayar
Christina Maeda Takiya
Mario Abbud-Filho
author_sort Heloisa Cristina Caldas
collection DOAJ
description 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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spelling doaj-art-348fc12c0f804570adc92c6edea2a34b2025-02-03T06:00:06ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/74283167428316Induced Pluripotent Stem Cells Reduce Progression of Experimental Chronic Kidney Disease but Develop Wilms’ TumorsHeloisa Cristina Caldas0Fernando Henrique Lojudice1Cinthia Dias2Ida Maria Maximina Fernandes-Charpiot3Maria Alice Sperto Ferreira Baptista4Rosa Sayoko Kawasaki-Oyama5Mari Cleide Sogayar6Christina Maeda Takiya7Mario Abbud-Filho8Laboratory of Immunology and Experimental Transplantation (LITEX), Department of Medicine FAMERP Medical School, Sao Jose do Rio Preto, SP, BrazilNUCEL-NETCEM Cell and Molecular Therapy Center, Medical Clinics Department, School of Medicine, University of São Paulo, Sao Paulo, SP, BrazilLaboratory of Immunology and Experimental Transplantation (LITEX), Department of Medicine FAMERP Medical School, Sao Jose do Rio Preto, SP, BrazilLaboratory of Immunology and Experimental Transplantation (LITEX), Department of Medicine FAMERP Medical School, Sao Jose do Rio Preto, SP, BrazilLaboratory of Immunology and Experimental Transplantation (LITEX), Department of Medicine FAMERP Medical School, Sao Jose do Rio Preto, SP, BrazilGenetics and Molecular Biology Research Unit Laboratory-UPGEM, FAMERP Medical School, Sao Jose do Rio Preto, SP, BrazilNUCEL-NETCEM Cell and Molecular Therapy Center, Medical Clinics Department, School of Medicine, University of São Paulo, Sao Paulo, SP, BrazilLaboratório de Imunopatologia, Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, RJ, BrazilLaboratory of Immunology and Experimental Transplantation (LITEX), Department of Medicine FAMERP Medical School, Sao Jose do Rio Preto, SP, BrazilThe 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.http://dx.doi.org/10.1155/2017/7428316
spellingShingle Heloisa Cristina Caldas
Fernando Henrique Lojudice
Cinthia Dias
Ida Maria Maximina Fernandes-Charpiot
Maria Alice Sperto Ferreira Baptista
Rosa Sayoko Kawasaki-Oyama
Mari Cleide Sogayar
Christina Maeda Takiya
Mario Abbud-Filho
Induced Pluripotent Stem Cells Reduce Progression of Experimental Chronic Kidney Disease but Develop Wilms’ Tumors
Stem Cells International
title Induced Pluripotent Stem Cells Reduce Progression of Experimental Chronic Kidney Disease but Develop Wilms’ Tumors
title_full Induced Pluripotent Stem Cells Reduce Progression of Experimental Chronic Kidney Disease but Develop Wilms’ Tumors
title_fullStr Induced Pluripotent Stem Cells Reduce Progression of Experimental Chronic Kidney Disease but Develop Wilms’ Tumors
title_full_unstemmed Induced Pluripotent Stem Cells Reduce Progression of Experimental Chronic Kidney Disease but Develop Wilms’ Tumors
title_short Induced Pluripotent Stem Cells Reduce Progression of Experimental Chronic Kidney Disease but Develop Wilms’ Tumors
title_sort induced pluripotent stem cells reduce progression of experimental chronic kidney disease but develop wilms tumors
url http://dx.doi.org/10.1155/2017/7428316
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