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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ishiy, Crysthiane Saveriano Rubiao Andre, Ormanji, Milene Subtil, Maquigussa, Edgar, Ribeiro, Rosemara Silva, da Silva Novaes, Antonio, Boim, Mirian Aparecida
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