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Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease

BACKGROUND: Chronic kidney disease (CKD) is a global public health problem. Cell therapy using pluripotent stem cells represents an attractive therapeutic approach for the treatment of CKD. METHODS: We transplanted mitomycin C (MMC)-treated human induced pluripotent stem cells (hiPSCs) and renal pro...

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Autores principales: Ribeiro, Patrícia de Carvalho, Lojudice, Fernando Henrique, Fernandes-Charpiot, Ida Maria Maximina, Baptista, Maria Alice Sperto Ferreira, de Almeida Araújo, Stanley, Mendes, Gloria Elisa Florido, Sogayar, Mari Cleide, Abbud-Filho, Mario, Caldas, Heloisa Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727202/
https://www.ncbi.nlm.nih.gov/pubmed/33298161
http://dx.doi.org/10.1186/s13287-020-02060-4
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author Ribeiro, Patrícia de Carvalho
Lojudice, Fernando Henrique
Fernandes-Charpiot, Ida Maria Maximina
Baptista, Maria Alice Sperto Ferreira
de Almeida Araújo, Stanley
Mendes, Gloria Elisa Florido
Sogayar, Mari Cleide
Abbud-Filho, Mario
Caldas, Heloisa Cristina
author_facet Ribeiro, Patrícia de Carvalho
Lojudice, Fernando Henrique
Fernandes-Charpiot, Ida Maria Maximina
Baptista, Maria Alice Sperto Ferreira
de Almeida Araújo, Stanley
Mendes, Gloria Elisa Florido
Sogayar, Mari Cleide
Abbud-Filho, Mario
Caldas, Heloisa Cristina
author_sort Ribeiro, Patrícia de Carvalho
collection PubMed
description BACKGROUND: Chronic kidney disease (CKD) is a global public health problem. Cell therapy using pluripotent stem cells represents an attractive therapeutic approach for the treatment of CKD. METHODS: We transplanted mitomycin C (MMC)-treated human induced pluripotent stem cells (hiPSCs) and renal progenitor cells (RPCs) into a CKD rat model system. The RPC and hiPSC cells were characterized by immunofluorescence and qRT-PCR. Untreated 5/6 nephrectomized rats were compared to CKD animals receiving the same amount of MMC-treated hiPSCs or RPCs. Renal function, histology, and immunohistochemistry were evaluated 45 days post-surgery. RESULTS: We successfully generated hiPSCs from peripheral blood and differentiated them into RPCs expressing renal progenitor genes (PAX2, WT1, SIX2, and SALL1) and podocyte-related genes (SYNPO, NPHS1). RPCs also exhibited reduced OCT4 expression, confirming the loss of pluripotency. After cell transplantation into CKD rats, the body weight change was significantly increased in both hiPSC and RPC groups, in comparison with the control group. Creatinine clearance (CCr) was preserved only in the hiPSC group. Similarly, the number of macrophages in the kidneys of the hiPSC group reached a statistically significant reduction, when compared to control rats. Both treatments reduced positive staining for the marker α-smooth muscle actin. Histological features showed decreased tubulointerstitial damage (interstitial fibrosis and tubular atrophy) as well as a reduction in glomerulosclerosis in both iPSC and RPC groups. CONCLUSIONS: In conclusion, we describe that both MMC-treated hiPSCs and RPCs exert beneficial effects in attenuating CKD progression. Both cell types were equally efficient to reduce histological damage and weight loss caused by CKD. hiPSCs seem to be more efficient than RPCs, possibly due to a paracrine effect triggered by hiPSCs. These results demonstrate that the use of MMC-treated hiPSCs and RPCs improves clinical and histological CKD parameters, avoided tumor formation, and therefore may be a promising cell therapy strategy for CKD. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-020-02060-4.
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spelling pubmed-77272022020-12-11 Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease Ribeiro, Patrícia de Carvalho Lojudice, Fernando Henrique Fernandes-Charpiot, Ida Maria Maximina Baptista, Maria Alice Sperto Ferreira de Almeida Araújo, Stanley Mendes, Gloria Elisa Florido Sogayar, Mari Cleide Abbud-Filho, Mario Caldas, Heloisa Cristina Stem Cell Res Ther Research BACKGROUND: Chronic kidney disease (CKD) is a global public health problem. Cell therapy using pluripotent stem cells represents an attractive therapeutic approach for the treatment of CKD. METHODS: We transplanted mitomycin C (MMC)-treated human induced pluripotent stem cells (hiPSCs) and renal progenitor cells (RPCs) into a CKD rat model system. The RPC and hiPSC cells were characterized by immunofluorescence and qRT-PCR. Untreated 5/6 nephrectomized rats were compared to CKD animals receiving the same amount of MMC-treated hiPSCs or RPCs. Renal function, histology, and immunohistochemistry were evaluated 45 days post-surgery. RESULTS: We successfully generated hiPSCs from peripheral blood and differentiated them into RPCs expressing renal progenitor genes (PAX2, WT1, SIX2, and SALL1) and podocyte-related genes (SYNPO, NPHS1). RPCs also exhibited reduced OCT4 expression, confirming the loss of pluripotency. After cell transplantation into CKD rats, the body weight change was significantly increased in both hiPSC and RPC groups, in comparison with the control group. Creatinine clearance (CCr) was preserved only in the hiPSC group. Similarly, the number of macrophages in the kidneys of the hiPSC group reached a statistically significant reduction, when compared to control rats. Both treatments reduced positive staining for the marker α-smooth muscle actin. Histological features showed decreased tubulointerstitial damage (interstitial fibrosis and tubular atrophy) as well as a reduction in glomerulosclerosis in both iPSC and RPC groups. CONCLUSIONS: In conclusion, we describe that both MMC-treated hiPSCs and RPCs exert beneficial effects in attenuating CKD progression. Both cell types were equally efficient to reduce histological damage and weight loss caused by CKD. hiPSCs seem to be more efficient than RPCs, possibly due to a paracrine effect triggered by hiPSCs. These results demonstrate that the use of MMC-treated hiPSCs and RPCs improves clinical and histological CKD parameters, avoided tumor formation, and therefore may be a promising cell therapy strategy for CKD. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-020-02060-4. BioMed Central 2020-12-09 /pmc/articles/PMC7727202/ /pubmed/33298161 http://dx.doi.org/10.1186/s13287-020-02060-4 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ribeiro, Patrícia de Carvalho
Lojudice, Fernando Henrique
Fernandes-Charpiot, Ida Maria Maximina
Baptista, Maria Alice Sperto Ferreira
de Almeida Araújo, Stanley
Mendes, Gloria Elisa Florido
Sogayar, Mari Cleide
Abbud-Filho, Mario
Caldas, Heloisa Cristina
Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease
title Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease
title_full Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease
title_fullStr Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease
title_full_unstemmed Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease
title_short Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease
title_sort therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727202/
https://www.ncbi.nlm.nih.gov/pubmed/33298161
http://dx.doi.org/10.1186/s13287-020-02060-4
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