Extracellular Vesicles (EVs) Derived from Mesenchymal Stem Cells (MSCs) as Adjuvants in the Treatment of Chronic Kidney Disease (CKD)

Chronic kidney disease (CKD) is considered an important health issue worldwide. The renin–angiotensin–aldosterone system (RAAS) blockade through the administration of angiotensin II receptor blockers, such as Losartan (LOS), has been considered the best strategy for CKD treatment for decades. Howeve...

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Main Authors: Paloma Noda, Ana L. R. Francini, Flavio Teles, Samuel J. Júnior, Fernando L. A. Fonseca, Fernanda T. Borges, Adão C. Sobrinho, Noemi Taniwaki, Irene L. Noronha, Camilla Fanelli
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Language:English
Published: MDPI AG 2025-03-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/6/434
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author Paloma Noda
Ana L. R. Francini
Flavio Teles
Samuel J. Júnior
Fernando L. A. Fonseca
Fernanda T. Borges
Adão C. Sobrinho
Noemi Taniwaki
Irene L. Noronha
Camilla Fanelli
author_facet Paloma Noda
Ana L. R. Francini
Flavio Teles
Samuel J. Júnior
Fernando L. A. Fonseca
Fernanda T. Borges
Adão C. Sobrinho
Noemi Taniwaki
Irene L. Noronha
Camilla Fanelli
author_sort Paloma Noda
collection DOAJ
description Chronic kidney disease (CKD) is considered an important health issue worldwide. The renin–angiotensin–aldosterone system (RAAS) blockade through the administration of angiotensin II receptor blockers, such as Losartan (LOS), has been considered the best strategy for CKD treatment for decades. However, this approach promotes only partial detention of CKD progression and cannot reverse renal damage. The aim of the present study was to investigate whether the therapeutic administration of extracellular vesicles (EVs) derived from adipose stem cells (ASCs), associated to LOS treatment, would promote additional renoprotection in rats underwent the 5/6 renal ablation CKD model. ASC-derived EV were administered locally, in the renal subcapsular area, 15 days after CKD induction, when LOS therapy also began. Animals were followed for additional 15 days and our results demonstrated that subcapsular injection of ASC-derived EV associated with LOS significantly reduced glomerulosclerosis, renal interstitial infiltration by myofibroblasts, and macrophages in the 5/6 CKD model. Additionally, LOS + EV abrogated systemic hypertension, proteinuria, and albuminuria, and stimulated local gene overexpression of the endogenous anti-inflammatory <i>Il-4</i>. Although more studies are still required to establish the best EV dose and administration route, these findings point to therapy with ASC-derived EV as a potential adjuvant in CKD treatment
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spelling doaj-art-c8000f3b29d8416fac52ddcd72735f4b2025-08-20T03:43:11ZengMDPI AGCells2073-44092025-03-0114643410.3390/cells14060434Extracellular Vesicles (EVs) Derived from Mesenchymal Stem Cells (MSCs) as Adjuvants in the Treatment of Chronic Kidney Disease (CKD)Paloma Noda0Ana L. R. Francini1Flavio Teles2Samuel J. Júnior3Fernando L. A. Fonseca4Fernanda T. Borges5Adão C. Sobrinho6Noemi Taniwaki7Irene L. Noronha8Camilla Fanelli9Laboratory of Cellular, Genetic and Molecular Nephrology, Renal Division, Faculty of Medicine, University of São Paulo, Av. Dr. Arnaldo, 455, 4° Andar, 4304, São Paulo 01246-903, SP, BrazilLaboratory of Cellular, Genetic and Molecular Nephrology, Renal Division, Faculty of Medicine, University of São Paulo, Av. Dr. Arnaldo, 455, 4° Andar, 4304, São Paulo 01246-903, SP, BrazilRenal Division, Faculty of Medicine, Federal University of Alagoas, Maceio 57200-000, AL, BrazilLaboratory of Cellular, Genetic and Molecular Nephrology, Renal Division, Faculty of Medicine, University of São Paulo, Av. Dr. Arnaldo, 455, 4° Andar, 4304, São Paulo 01246-903, SP, BrazilDepartment of Clinical Laboratory, University Center of ABC Medical School, Santo Andre 09060-650, SP, BrazilDepartament of Medicine, Nephrology Division, Paulista School of Medicine, Federal University of São Paulo, São Paulo 04023-062, SP, BrazilLaboratory of Cellular Biology, Department of Pathology, School of Medicine, University of São Paulo, São Paulo 01246-903, SP, BrazilLaboratory of Electron Microscopy, Instituto Adolfo Lutz, São Paulo 01246-000, SP, BrazilLaboratory of Cellular, Genetic and Molecular Nephrology, Renal Division, Faculty of Medicine, University of São Paulo, Av. Dr. Arnaldo, 455, 4° Andar, 4304, São Paulo 01246-903, SP, BrazilLaboratory of Cellular, Genetic and Molecular Nephrology, Renal Division, Faculty of Medicine, University of São Paulo, Av. Dr. Arnaldo, 455, 4° Andar, 4304, São Paulo 01246-903, SP, BrazilChronic kidney disease (CKD) is considered an important health issue worldwide. The renin–angiotensin–aldosterone system (RAAS) blockade through the administration of angiotensin II receptor blockers, such as Losartan (LOS), has been considered the best strategy for CKD treatment for decades. However, this approach promotes only partial detention of CKD progression and cannot reverse renal damage. The aim of the present study was to investigate whether the therapeutic administration of extracellular vesicles (EVs) derived from adipose stem cells (ASCs), associated to LOS treatment, would promote additional renoprotection in rats underwent the 5/6 renal ablation CKD model. ASC-derived EV were administered locally, in the renal subcapsular area, 15 days after CKD induction, when LOS therapy also began. Animals were followed for additional 15 days and our results demonstrated that subcapsular injection of ASC-derived EV associated with LOS significantly reduced glomerulosclerosis, renal interstitial infiltration by myofibroblasts, and macrophages in the 5/6 CKD model. Additionally, LOS + EV abrogated systemic hypertension, proteinuria, and albuminuria, and stimulated local gene overexpression of the endogenous anti-inflammatory <i>Il-4</i>. Although more studies are still required to establish the best EV dose and administration route, these findings point to therapy with ASC-derived EV as a potential adjuvant in CKD treatmenthttps://www.mdpi.com/2073-4409/14/6/434extracellular vesicleschronic kidney diseasecell therapymesenchymal stem cells
spellingShingle Paloma Noda
Ana L. R. Francini
Flavio Teles
Samuel J. Júnior
Fernando L. A. Fonseca
Fernanda T. Borges
Adão C. Sobrinho
Noemi Taniwaki
Irene L. Noronha
Camilla Fanelli
Extracellular Vesicles (EVs) Derived from Mesenchymal Stem Cells (MSCs) as Adjuvants in the Treatment of Chronic Kidney Disease (CKD)
Cells
extracellular vesicles
chronic kidney disease
cell therapy
mesenchymal stem cells
title Extracellular Vesicles (EVs) Derived from Mesenchymal Stem Cells (MSCs) as Adjuvants in the Treatment of Chronic Kidney Disease (CKD)
title_full Extracellular Vesicles (EVs) Derived from Mesenchymal Stem Cells (MSCs) as Adjuvants in the Treatment of Chronic Kidney Disease (CKD)
title_fullStr Extracellular Vesicles (EVs) Derived from Mesenchymal Stem Cells (MSCs) as Adjuvants in the Treatment of Chronic Kidney Disease (CKD)
title_full_unstemmed Extracellular Vesicles (EVs) Derived from Mesenchymal Stem Cells (MSCs) as Adjuvants in the Treatment of Chronic Kidney Disease (CKD)
title_short Extracellular Vesicles (EVs) Derived from Mesenchymal Stem Cells (MSCs) as Adjuvants in the Treatment of Chronic Kidney Disease (CKD)
title_sort extracellular vesicles evs derived from mesenchymal stem cells mscs as adjuvants in the treatment of chronic kidney disease ckd
topic extracellular vesicles
chronic kidney disease
cell therapy
mesenchymal stem cells
url https://www.mdpi.com/2073-4409/14/6/434
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