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Exploring macrophage cell therapy on Diabetic Kidney Disease
Alternatively activated macrophages (M2) have regenerative properties and shown promise as cell therapy in chronic kidney disease. However, M2 plasticity is one of the major hurdles to overcome. Our previous studies showed that genetically modified macrophages stabilized by neutrophil gelatinase‐ass...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349346/ https://www.ncbi.nlm.nih.gov/pubmed/30407737 http://dx.doi.org/10.1111/jcmm.13983 |
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author | Guiteras, Roser Sola, Anna Flaquer, Maria Manonelles, Anna Hotter, Georgina Cruzado, Josep M. |
author_facet | Guiteras, Roser Sola, Anna Flaquer, Maria Manonelles, Anna Hotter, Georgina Cruzado, Josep M. |
author_sort | Guiteras, Roser |
collection | PubMed |
description | Alternatively activated macrophages (M2) have regenerative properties and shown promise as cell therapy in chronic kidney disease. However, M2 plasticity is one of the major hurdles to overcome. Our previous studies showed that genetically modified macrophages stabilized by neutrophil gelatinase‐associated lipocalin (NGAL) were able to preserve their M2 phenotype. Nowadays, little is known about M2 macrophage effects in diabetic kidney disease (DKD). The aim of the study was to investigate the therapeutic effect of both bone marrow‐derived M2 (BM‐фM2) and ф‐NGAL macrophages in the db/db mice. Seventeen‐week‐old mice with established DKD were divided into five treatment groups with their controls: D+BM‐фM2; D+ф‐BM; D+ф‐NGAL; D+ф‐RAW; D+SHAM and non‐diabetic (ND) (db/‐ and C57bl/6J) animals. We infused 1 × 10(6) macrophages twice, at baseline and 2 weeks thereafter. BM‐фM2 did not show any therapeutic effect whereas ф‐NGAL significantly reduced albuminuria and renal fibrosis. The ф‐NGAL therapy increased the anti‐inflammatory IL‐10 and reduced some pro‐inflammatory cytokines, reduced the proportion of M1 glomerular macrophages and podocyte loss and was associated with a significant decrease of renal TGF‐β1. Overall, our study provides evidence that ф‐NGAL macrophage cell therapy has a therapeutic effect on DKD probably by modulation of the renal inflammatory response caused by the diabetic milieu. |
format | Online Article Text |
id | pubmed-6349346 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63493462019-02-01 Exploring macrophage cell therapy on Diabetic Kidney Disease Guiteras, Roser Sola, Anna Flaquer, Maria Manonelles, Anna Hotter, Georgina Cruzado, Josep M. J Cell Mol Med Original Articles Alternatively activated macrophages (M2) have regenerative properties and shown promise as cell therapy in chronic kidney disease. However, M2 plasticity is one of the major hurdles to overcome. Our previous studies showed that genetically modified macrophages stabilized by neutrophil gelatinase‐associated lipocalin (NGAL) were able to preserve their M2 phenotype. Nowadays, little is known about M2 macrophage effects in diabetic kidney disease (DKD). The aim of the study was to investigate the therapeutic effect of both bone marrow‐derived M2 (BM‐фM2) and ф‐NGAL macrophages in the db/db mice. Seventeen‐week‐old mice with established DKD were divided into five treatment groups with their controls: D+BM‐фM2; D+ф‐BM; D+ф‐NGAL; D+ф‐RAW; D+SHAM and non‐diabetic (ND) (db/‐ and C57bl/6J) animals. We infused 1 × 10(6) macrophages twice, at baseline and 2 weeks thereafter. BM‐фM2 did not show any therapeutic effect whereas ф‐NGAL significantly reduced albuminuria and renal fibrosis. The ф‐NGAL therapy increased the anti‐inflammatory IL‐10 and reduced some pro‐inflammatory cytokines, reduced the proportion of M1 glomerular macrophages and podocyte loss and was associated with a significant decrease of renal TGF‐β1. Overall, our study provides evidence that ф‐NGAL macrophage cell therapy has a therapeutic effect on DKD probably by modulation of the renal inflammatory response caused by the diabetic milieu. John Wiley and Sons Inc. 2018-11-08 2019-02 /pmc/articles/PMC6349346/ /pubmed/30407737 http://dx.doi.org/10.1111/jcmm.13983 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Guiteras, Roser Sola, Anna Flaquer, Maria Manonelles, Anna Hotter, Georgina Cruzado, Josep M. Exploring macrophage cell therapy on Diabetic Kidney Disease |
title | Exploring macrophage cell therapy on Diabetic Kidney Disease |
title_full | Exploring macrophage cell therapy on Diabetic Kidney Disease |
title_fullStr | Exploring macrophage cell therapy on Diabetic Kidney Disease |
title_full_unstemmed | Exploring macrophage cell therapy on Diabetic Kidney Disease |
title_short | Exploring macrophage cell therapy on Diabetic Kidney Disease |
title_sort | exploring macrophage cell therapy on diabetic kidney disease |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349346/ https://www.ncbi.nlm.nih.gov/pubmed/30407737 http://dx.doi.org/10.1111/jcmm.13983 |
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