Nephroprotective Potential of Mesenchymal Stromal Cells and Their Extracellular Vesicles in a Murine Model of Chronic Cyclosporine Nephrotoxicity

Cell therapies and derived products have a high potential in aiding tissue and organ repairing and have therefore been considered as potential therapies for treating renal diseases. However, few studies have evaluated the impact of these therapies according to the stage of chronic kidney disease. Th...

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Autores: Ramírez Bajo, María José, Martin Ramírez, Javier, Bruno, Stefania, Pasquino, Chiara, Bañón Maneus, Elisenda, Rovira Juárez, Jordi, Moya Rull, Daniel, Lazo Rodríguez, Marta, Campistol Plana, Josep M., Camussi, Giovanni, Diekmann, Fritz
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/224638
Acesso em linha:https://hdl.handle.net/2445/224638
Access Level:acceso abierto
Palavra-chave:Cèl·lules mare
Medicina regenerativa
Trasplantament renal
Stem cells
Regenerative medicine
Kidney transplantation
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spelling Nephroprotective Potential of Mesenchymal Stromal Cells and Their Extracellular Vesicles in a Murine Model of Chronic Cyclosporine NephrotoxicityRamírez Bajo, María JoséMartin Ramírez, JavierBruno, StefaniaPasquino, ChiaraBañón Maneus, Elisenda Rovira Juárez, Jordi Moya Rull, Daniel Lazo Rodríguez, Marta Campistol Plana, Josep M. Camussi, GiovanniDiekmann, FritzCèl·lules mareMedicina regenerativaTrasplantament renalStem cellsRegenerative medicineKidney transplantationCell therapies and derived products have a high potential in aiding tissue and organ repairing and have therefore been considered as potential therapies for treating renal diseases. However, few studies have evaluated the impact of these therapies according to the stage of chronic kidney disease. The aim of this study was to evaluate the renoprotective effect of murine bone marrow mesenchymal stromal cells (BM-MSCs), their extracellular vesicles (EVs) and EVs-depleted conditioned medium (dCM) in an aggressive mouse model of chronic cyclosporine (CsA) nephrotoxicity in a preventive and curative manner. Methods: After 4 weeks of CsA-treatment (75 mg/kg daily) mice developed severe nephrotoxicity associated with a poor survival rate of 25%, and characterized by tubular vacuolization, casts, and cysts in renal histology. BM-MSC, EVs and dCM groups were administered as prophylaxis or as treatment of CsA nephrotoxicity. The effect of the cell therapies was analyzed by assessing renal function, histological damage, apoptotic cell death, and gene expression of fibrotic mediators. Results: Combined administration of CsA and BM-MSCs ameliorated the mice survival rates (6–15%), but significantly renal function, and histological parameters, translating into a reduction of apoptosis and fibrotic markers. On the other hand, EVs and dCM administration were only associated with a partial recovery of renal function or histological damage. Better results were obtained when used as treatment rather than as prophylactic regimen i.e., cell therapy was more effective once the damage was established. Conclusion: In this study, we showed that BM-MSCs induce an improvement in renal outcomes in an animal model of CsA nephrotoxicity, particularly if the inflammatory microenvironment is already established. EVs and dCM treatment induce a partial recovery, indicating that further experiments are required to adjust timing and dose for better long-term outcomes.Frontiers Media2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/224638Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fcell.2020.00296Frontiers In Cell And Developmental Biology, 2020, vol. 8, 296https://doi.org/10.3389/fcell.2020.00296cc-by (c) Ramírez Bajo, María José et al., 2020https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2246382026-05-27T06:46:51Z
dc.title.none.fl_str_mv Nephroprotective Potential of Mesenchymal Stromal Cells and Their Extracellular Vesicles in a Murine Model of Chronic Cyclosporine Nephrotoxicity
title Nephroprotective Potential of Mesenchymal Stromal Cells and Their Extracellular Vesicles in a Murine Model of Chronic Cyclosporine Nephrotoxicity
spellingShingle Nephroprotective Potential of Mesenchymal Stromal Cells and Their Extracellular Vesicles in a Murine Model of Chronic Cyclosporine Nephrotoxicity
Ramírez Bajo, María José
Cèl·lules mare
Medicina regenerativa
Trasplantament renal
Stem cells
Regenerative medicine
Kidney transplantation
title_short Nephroprotective Potential of Mesenchymal Stromal Cells and Their Extracellular Vesicles in a Murine Model of Chronic Cyclosporine Nephrotoxicity
title_full Nephroprotective Potential of Mesenchymal Stromal Cells and Their Extracellular Vesicles in a Murine Model of Chronic Cyclosporine Nephrotoxicity
title_fullStr Nephroprotective Potential of Mesenchymal Stromal Cells and Their Extracellular Vesicles in a Murine Model of Chronic Cyclosporine Nephrotoxicity
title_full_unstemmed Nephroprotective Potential of Mesenchymal Stromal Cells and Their Extracellular Vesicles in a Murine Model of Chronic Cyclosporine Nephrotoxicity
title_sort Nephroprotective Potential of Mesenchymal Stromal Cells and Their Extracellular Vesicles in a Murine Model of Chronic Cyclosporine Nephrotoxicity
dc.creator.none.fl_str_mv Ramírez Bajo, María José
Martin Ramírez, Javier
Bruno, Stefania
Pasquino, Chiara
Bañón Maneus, Elisenda
Rovira Juárez, Jordi
Moya Rull, Daniel
Lazo Rodríguez, Marta
Campistol Plana, Josep M.
Camussi, Giovanni
Diekmann, Fritz
author Ramírez Bajo, María José
author_facet Ramírez Bajo, María José
Martin Ramírez, Javier
Bruno, Stefania
Pasquino, Chiara
Bañón Maneus, Elisenda
Rovira Juárez, Jordi
Moya Rull, Daniel
Lazo Rodríguez, Marta
Campistol Plana, Josep M.
Camussi, Giovanni
Diekmann, Fritz
author_role author
author2 Martin Ramírez, Javier
Bruno, Stefania
Pasquino, Chiara
Bañón Maneus, Elisenda
Rovira Juárez, Jordi
Moya Rull, Daniel
Lazo Rodríguez, Marta
Campistol Plana, Josep M.
Camussi, Giovanni
Diekmann, Fritz
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cèl·lules mare
Medicina regenerativa
Trasplantament renal
Stem cells
Regenerative medicine
Kidney transplantation
topic Cèl·lules mare
Medicina regenerativa
Trasplantament renal
Stem cells
Regenerative medicine
Kidney transplantation
description Cell therapies and derived products have a high potential in aiding tissue and organ repairing and have therefore been considered as potential therapies for treating renal diseases. However, few studies have evaluated the impact of these therapies according to the stage of chronic kidney disease. The aim of this study was to evaluate the renoprotective effect of murine bone marrow mesenchymal stromal cells (BM-MSCs), their extracellular vesicles (EVs) and EVs-depleted conditioned medium (dCM) in an aggressive mouse model of chronic cyclosporine (CsA) nephrotoxicity in a preventive and curative manner. Methods: After 4 weeks of CsA-treatment (75 mg/kg daily) mice developed severe nephrotoxicity associated with a poor survival rate of 25%, and characterized by tubular vacuolization, casts, and cysts in renal histology. BM-MSC, EVs and dCM groups were administered as prophylaxis or as treatment of CsA nephrotoxicity. The effect of the cell therapies was analyzed by assessing renal function, histological damage, apoptotic cell death, and gene expression of fibrotic mediators. Results: Combined administration of CsA and BM-MSCs ameliorated the mice survival rates (6–15%), but significantly renal function, and histological parameters, translating into a reduction of apoptosis and fibrotic markers. On the other hand, EVs and dCM administration were only associated with a partial recovery of renal function or histological damage. Better results were obtained when used as treatment rather than as prophylactic regimen i.e., cell therapy was more effective once the damage was established. Conclusion: In this study, we showed that BM-MSCs induce an improvement in renal outcomes in an animal model of CsA nephrotoxicity, particularly if the inflammatory microenvironment is already established. EVs and dCM treatment induce a partial recovery, indicating that further experiments are required to adjust timing and dose for better long-term outcomes.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/224638
url https://hdl.handle.net/2445/224638
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fcell.2020.00296
Frontiers In Cell And Developmental Biology, 2020, vol. 8, 296
https://doi.org/10.3389/fcell.2020.00296
dc.rights.none.fl_str_mv cc-by (c) Ramírez Bajo, María José et al., 2020
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Ramírez Bajo, María José et al., 2020
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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