Comparison of the Effects of Mesenchymal Stem Cells with Their Extracellular Vesicles on the Treatment of Kidney Damage Induced by Chronic Renal Artery Stenosis
BACKGROUND: Chronic renal artery stenosis is considered one of the most common causes of renovascular hypertension (RH). Chronic hypoxia can lead to irreversible damage to renal tissue and to a progressive deterioration of renal function. We have previously shown that bone marrow-derived mesenchymal...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568167/ https://www.ncbi.nlm.nih.gov/pubmed/33101418 http://dx.doi.org/10.1155/2020/8814574 |
_version_ | 1783596474648494080 |
---|---|
author | Ishiy, Crysthiane Saveriano Rubiao Andre Ormanji, Milene Subtil Maquigussa, Edgar Ribeiro, Rosemara Silva da Silva Novaes, Antonio Boim, Mirian Aparecida |
author_facet | Ishiy, Crysthiane Saveriano Rubiao Andre Ormanji, Milene Subtil Maquigussa, Edgar Ribeiro, Rosemara Silva da Silva Novaes, Antonio Boim, Mirian Aparecida |
author_sort | Ishiy, Crysthiane Saveriano Rubiao Andre |
collection | PubMed |
description | BACKGROUND: Chronic renal artery stenosis is considered one of the most common causes of renovascular hypertension (RH). Chronic hypoxia can lead to irreversible damage to renal tissue and to a progressive deterioration of renal function. We have previously shown that bone marrow-derived mesenchymal stem cells (BMSCs) improved renal parenchyma and function in a model of RH (2 kidneys, 1 clip model (2K-1C) in rats. Microvesicles (MVs) and exosomes (EXs) released by MSCs have been shown to induce effects similar to those induced by whole cells but with fewer side effects. In this study, we compared the effects of adipose-derived MSCs (ASCs) with those of the MVs and EXs released by ASCs on tissue inflammation and renal function in 2 K-1C rats. RESULTS: Flow cytometry analysis showed that even after 15 days, ASCs were still detected in both kidneys. The expression of a stem cell homing marker (SDF1-α) was increased in ASC-treated animals in both the stenotic and contralateral kidneys. Interestingly, SDF1-α expression was also increased in MV- and EX-treated animals. A hypoxia marker (HIF1-α) was upregulated in the stenotic kidney, and treatments with ASCs, MVs, and EXs were effective in reducing the expression of this marker. Stenotic animals showed a progressive increase in systolic blood pressure (SBP), while animals treated with ASCs, MVs, and EXs showed a stabilization of SBP, and this stabilization was similar among the different treatments. Stenotic animals developed significant proteinuria, which was reduced by ASCs and MVs but not by EXs. The increased expression of Col I and TGFβ in both kidneys was reduced by all the treatments, and these treatments also effectively increased the expression of the anti-inflammatory cytokine IL-10 in both kidneys; however, only ASCs were able to reduce the overexpression of the proinflammatory cytokine IL-1β in both kidneys of 2K-1C animals. CONCLUSION: The results of this study demonstrated that the EVs released by ASCs produced beneficial results but with lower efficacy than whole cells. ASCs produced stronger effects in this model of renal chronic hypoxia, and the use of EVs instead of whole cells should be evaluated depending on the parameter to be corrected. |
format | Online Article Text |
id | pubmed-7568167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-75681672020-10-22 Comparison of the Effects of Mesenchymal Stem Cells with Their Extracellular Vesicles on the Treatment of Kidney Damage Induced by Chronic Renal Artery Stenosis Ishiy, Crysthiane Saveriano Rubiao Andre Ormanji, Milene Subtil Maquigussa, Edgar Ribeiro, Rosemara Silva da Silva Novaes, Antonio Boim, Mirian Aparecida Stem Cells Int Research Article BACKGROUND: Chronic renal artery stenosis is considered one of the most common causes of renovascular hypertension (RH). Chronic hypoxia can lead to irreversible damage to renal tissue and to a progressive deterioration of renal function. We have previously shown that bone marrow-derived mesenchymal stem cells (BMSCs) improved renal parenchyma and function in a model of RH (2 kidneys, 1 clip model (2K-1C) in rats. Microvesicles (MVs) and exosomes (EXs) released by MSCs have been shown to induce effects similar to those induced by whole cells but with fewer side effects. In this study, we compared the effects of adipose-derived MSCs (ASCs) with those of the MVs and EXs released by ASCs on tissue inflammation and renal function in 2 K-1C rats. RESULTS: Flow cytometry analysis showed that even after 15 days, ASCs were still detected in both kidneys. The expression of a stem cell homing marker (SDF1-α) was increased in ASC-treated animals in both the stenotic and contralateral kidneys. Interestingly, SDF1-α expression was also increased in MV- and EX-treated animals. A hypoxia marker (HIF1-α) was upregulated in the stenotic kidney, and treatments with ASCs, MVs, and EXs were effective in reducing the expression of this marker. Stenotic animals showed a progressive increase in systolic blood pressure (SBP), while animals treated with ASCs, MVs, and EXs showed a stabilization of SBP, and this stabilization was similar among the different treatments. Stenotic animals developed significant proteinuria, which was reduced by ASCs and MVs but not by EXs. The increased expression of Col I and TGFβ in both kidneys was reduced by all the treatments, and these treatments also effectively increased the expression of the anti-inflammatory cytokine IL-10 in both kidneys; however, only ASCs were able to reduce the overexpression of the proinflammatory cytokine IL-1β in both kidneys of 2K-1C animals. CONCLUSION: The results of this study demonstrated that the EVs released by ASCs produced beneficial results but with lower efficacy than whole cells. ASCs produced stronger effects in this model of renal chronic hypoxia, and the use of EVs instead of whole cells should be evaluated depending on the parameter to be corrected. Hindawi 2020-10-08 /pmc/articles/PMC7568167/ /pubmed/33101418 http://dx.doi.org/10.1155/2020/8814574 Text en Copyright © 2020 Crysthiane Saveriano Rubiao Andre Ishiy et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Ishiy, Crysthiane Saveriano Rubiao Andre Ormanji, Milene Subtil Maquigussa, Edgar Ribeiro, Rosemara Silva da Silva Novaes, Antonio Boim, Mirian Aparecida Comparison of the Effects of Mesenchymal Stem Cells with Their Extracellular Vesicles on the Treatment of Kidney Damage Induced by Chronic Renal Artery Stenosis |
title | Comparison of the Effects of Mesenchymal Stem Cells with Their Extracellular Vesicles on the Treatment of Kidney Damage Induced by Chronic Renal Artery Stenosis |
title_full | Comparison of the Effects of Mesenchymal Stem Cells with Their Extracellular Vesicles on the Treatment of Kidney Damage Induced by Chronic Renal Artery Stenosis |
title_fullStr | Comparison of the Effects of Mesenchymal Stem Cells with Their Extracellular Vesicles on the Treatment of Kidney Damage Induced by Chronic Renal Artery Stenosis |
title_full_unstemmed | Comparison of the Effects of Mesenchymal Stem Cells with Their Extracellular Vesicles on the Treatment of Kidney Damage Induced by Chronic Renal Artery Stenosis |
title_short | Comparison of the Effects of Mesenchymal Stem Cells with Their Extracellular Vesicles on the Treatment of Kidney Damage Induced by Chronic Renal Artery Stenosis |
title_sort | comparison of the effects of mesenchymal stem cells with their extracellular vesicles on the treatment of kidney damage induced by chronic renal artery stenosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568167/ https://www.ncbi.nlm.nih.gov/pubmed/33101418 http://dx.doi.org/10.1155/2020/8814574 |
work_keys_str_mv | AT ishiycrysthianesaverianorubiaoandre comparisonoftheeffectsofmesenchymalstemcellswiththeirextracellularvesiclesonthetreatmentofkidneydamageinducedbychronicrenalarterystenosis AT ormanjimilenesubtil comparisonoftheeffectsofmesenchymalstemcellswiththeirextracellularvesiclesonthetreatmentofkidneydamageinducedbychronicrenalarterystenosis AT maquigussaedgar comparisonoftheeffectsofmesenchymalstemcellswiththeirextracellularvesiclesonthetreatmentofkidneydamageinducedbychronicrenalarterystenosis AT ribeirorosemarasilva comparisonoftheeffectsofmesenchymalstemcellswiththeirextracellularvesiclesonthetreatmentofkidneydamageinducedbychronicrenalarterystenosis AT dasilvanovaesantonio comparisonoftheeffectsofmesenchymalstemcellswiththeirextracellularvesiclesonthetreatmentofkidneydamageinducedbychronicrenalarterystenosis AT boimmirianaparecida comparisonoftheeffectsofmesenchymalstemcellswiththeirextracellularvesiclesonthetreatmentofkidneydamageinducedbychronicrenalarterystenosis |