PBMC therapy reduces cell death and tissue fibrosis after acute kidney injury by modulating the pattern of monocyte/macrophage survival in tissue

In this study, we investigated if the therapeutic potential of peripheral blood mononuclear cell (PBMC) therapy in a murine model of ischemic AKI is related with the survival pattern of monocyte/macrophages in tissue. CD-1 mice were subjected to bilateral renal ischemia followed by reperfusion to in...

Descripción completa

Detalles Bibliográficos
Autores: Torrico, Selene, Hotter, Georgina, Muñoz, Ángeles, Calle, Priscila, García, Miriam R., Poch, Esteban, Játiva, Soraya
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/374241
Acceso en línea:http://hdl.handle.net/10261/374241
https://api.elsevier.com/content/abstract/scopus_id/85199437826
Access Level:acceso abierto
Palabra clave:Acute kidney injure
Cell death
Inflammation
Macrophage
Monocyte
id ES_0664d85b30fbadfb1b0337cfb4f3eebe
oai_identifier_str oai:digital.csic.es:10261/374241
network_acronym_str ES
network_name_str España
repository_id_str
spelling PBMC therapy reduces cell death and tissue fibrosis after acute kidney injury by modulating the pattern of monocyte/macrophage survival in tissueTorrico, SeleneHotter, GeorginaMuñoz, ÁngelesCalle, PriscilaGarcía, Miriam R.Poch, EstebanJátiva, SorayaAcute kidney injureCell deathInflammationMacrophageMonocyteIn this study, we investigated if the therapeutic potential of peripheral blood mononuclear cell (PBMC) therapy in a murine model of ischemic AKI is related with the survival pattern of monocyte/macrophages in tissue. CD-1 mice were subjected to bilateral renal ischemia followed by reperfusion to induce AKI. M2-polarized PBMCs isolated from CD-1 mice were administered intravenously at different time points post-injury. Our results demonstrate that early administration of PBMC therapy attenuates renal tissue damage, reduces tissue cell death and prevents fibrosis development. Reduction of tissue pyroptosis was observed by reduction on NLRP3 inflammasome activation and decreasing IL-1beta and Caspase-1 expression in the kidney. Furthermore, the therapy was shown to mitigate ferroptosis by inducing GPX4 overexpression. Early administration of PBMCs increased the survival pattern of renal tissue-macrophages, promoting a "pro-survival phenotype" resulting in decreased pyroptotic marker NLRP3, IL-1beta and Caspase 1 and increased anti-ferroptotic gene GPX4. Conversely, delayed administration of PBMC therapy exhibits diminished efficacy in preventing cell death and fibrosis in tissue and provoked a decrease in the pro-survival phenotype of both monocyte /macrophages in tissue. Our findings highlight the therapeutic potential of PBMC therapy in mitigating AKI and preventing CKD progression by modulating tissue-resident macrophage survival and reducing their cell death pathways. The fact that the effectiveness of the therapy depends on the time of administration after the injury underscores the importance of early intervention in AKI management.The work is supported by grant from the Spanish Ministry of Economy and Competitiveness/Instituto de Salud Carlos III–Fondo Europeo de Desarrollo Regional (FEDER; PI20/00900) awarded to G.H., and by grant CPP2022-009582 funded by MCIN/AEI /10.13039/501100011033 and European Union Next Generation EU/ PRTR awarded to G.H.Peer reviewedElsevierInstituto de Salud Carlos IIIMinisterio de Economía y Competitividad (España)Agencia Estatal de Investigación (España)European CommissionTorrico, Selene [0000-0002-6734-003X]Hotter, Georgina [0000-0001-7324-1305]Calle, Priscila [0000-0001-9872-8013]Poch, Esteban [0000-0002-6492-024X]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/374241https://api.elsevier.com/content/abstract/scopus_id/85199437826reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CPP2022-009582The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1016/j.biopha.2024.117186https://doi.org/10.1016/j.biopha.2024.117186Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3742412026-05-22T06:33:51Z
dc.title.none.fl_str_mv PBMC therapy reduces cell death and tissue fibrosis after acute kidney injury by modulating the pattern of monocyte/macrophage survival in tissue
title PBMC therapy reduces cell death and tissue fibrosis after acute kidney injury by modulating the pattern of monocyte/macrophage survival in tissue
spellingShingle PBMC therapy reduces cell death and tissue fibrosis after acute kidney injury by modulating the pattern of monocyte/macrophage survival in tissue
Torrico, Selene
Acute kidney injure
Cell death
Inflammation
Macrophage
Monocyte
title_short PBMC therapy reduces cell death and tissue fibrosis after acute kidney injury by modulating the pattern of monocyte/macrophage survival in tissue
title_full PBMC therapy reduces cell death and tissue fibrosis after acute kidney injury by modulating the pattern of monocyte/macrophage survival in tissue
title_fullStr PBMC therapy reduces cell death and tissue fibrosis after acute kidney injury by modulating the pattern of monocyte/macrophage survival in tissue
title_full_unstemmed PBMC therapy reduces cell death and tissue fibrosis after acute kidney injury by modulating the pattern of monocyte/macrophage survival in tissue
title_sort PBMC therapy reduces cell death and tissue fibrosis after acute kidney injury by modulating the pattern of monocyte/macrophage survival in tissue
dc.creator.none.fl_str_mv Torrico, Selene
Hotter, Georgina
Muñoz, Ángeles
Calle, Priscila
García, Miriam R.
Poch, Esteban
Játiva, Soraya
author Torrico, Selene
author_facet Torrico, Selene
Hotter, Georgina
Muñoz, Ángeles
Calle, Priscila
García, Miriam R.
Poch, Esteban
Játiva, Soraya
author_role author
author2 Hotter, Georgina
Muñoz, Ángeles
Calle, Priscila
García, Miriam R.
Poch, Esteban
Játiva, Soraya
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Ministerio de Economía y Competitividad (España)
Agencia Estatal de Investigación (España)
European Commission
Torrico, Selene [0000-0002-6734-003X]
Hotter, Georgina [0000-0001-7324-1305]
Calle, Priscila [0000-0001-9872-8013]
Poch, Esteban [0000-0002-6492-024X]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Acute kidney injure
Cell death
Inflammation
Macrophage
Monocyte
topic Acute kidney injure
Cell death
Inflammation
Macrophage
Monocyte
description In this study, we investigated if the therapeutic potential of peripheral blood mononuclear cell (PBMC) therapy in a murine model of ischemic AKI is related with the survival pattern of monocyte/macrophages in tissue. CD-1 mice were subjected to bilateral renal ischemia followed by reperfusion to induce AKI. M2-polarized PBMCs isolated from CD-1 mice were administered intravenously at different time points post-injury. Our results demonstrate that early administration of PBMC therapy attenuates renal tissue damage, reduces tissue cell death and prevents fibrosis development. Reduction of tissue pyroptosis was observed by reduction on NLRP3 inflammasome activation and decreasing IL-1beta and Caspase-1 expression in the kidney. Furthermore, the therapy was shown to mitigate ferroptosis by inducing GPX4 overexpression. Early administration of PBMCs increased the survival pattern of renal tissue-macrophages, promoting a "pro-survival phenotype" resulting in decreased pyroptotic marker NLRP3, IL-1beta and Caspase 1 and increased anti-ferroptotic gene GPX4. Conversely, delayed administration of PBMC therapy exhibits diminished efficacy in preventing cell death and fibrosis in tissue and provoked a decrease in the pro-survival phenotype of both monocyte /macrophages in tissue. Our findings highlight the therapeutic potential of PBMC therapy in mitigating AKI and preventing CKD progression by modulating tissue-resident macrophage survival and reducing their cell death pathways. The fact that the effectiveness of the therapy depends on the time of administration after the injury underscores the importance of early intervention in AKI management.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/374241
https://api.elsevier.com/content/abstract/scopus_id/85199437826
url http://hdl.handle.net/10261/374241
https://api.elsevier.com/content/abstract/scopus_id/85199437826
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CPP2022-009582
The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1016/j.biopha.2024.117186
https://doi.org/10.1016/j.biopha.2024.117186
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869402915208167424
score 15,81155

Similares en LA Referencia