Circulating extracellular vesicles promote recovery in a preclinical model of intracerebral hemorrhage.

MT: Special Issue - Exploiting Extracellular Vesicles as Therapeutic Agents brain repair extracellular vesicles intracerebral hemorrhage preclinical studies proteomics safety treatment

Journal

Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621

Informations de publication

Date de publication:
13 Jun 2023
Historique:
received: 10 12 2022
accepted: 16 03 2023
medline: 24 4 2023
pubmed: 24 4 2023
entrez: 24 04 2023
Statut: epublish

Résumé

Circulating extracellular vesicles (EVs) are proposed to participate in enhancing pathways of recovery after stroke through paracrine signaling. To verify this hypothesis in a proof-of-concept study, blood-derived allogenic EVs from rats and xenogenic EVs from humans who experienced spontaneous good recovery after an intracerebral hemorrhage (ICH) were administered intravenously to rats at 24 h after a subcortical ICH. At 28 days, both treatments improved the motor function assessment scales score, showed greater fiber preservation in the perilesional zone (diffusion tensor-fractional anisotropy MRI), increased immunofluorescence markers of myelin (MOG), and decreased astrocyte markers (GFAP) compared with controls. Comparison of the protein cargo of circulating EVs at 28 days from animals with good vs. poor recovery showed down-expression of immune system activation pathways (CO4, KLKB1, PROC, FA9, and C1QA) and of restorative processes such as axon guidance (RAC1), myelination (MBP), and synaptic vesicle trafficking (SYN1), which is in line with better tissue preservation. Up-expression of PCSK9 (neuron differentiation) in xenogenic EVs-treated animals suggests enhancement of repair pathways. In conclusion, the administration of blood-derived EVs improved recovery after ICH. These findings open a new and promising opportunity for further development of restorative therapies to improve the outcomes after an ICH.

Identifiants

DOI: 10.1016/j.omtn.2023.03.006 PMID: 37090418 PMC: PMC10113711
pubmed: 37090418
doi: 10.1016/j.omtn.2023.03.006
pii: S2162-2531(23)00065-3
pmc: PMC10113711
doi:

Types de publication

Journal Article

Langues

eng

Pagination

247-262

Informations de copyright

© 2023 The Author(s).

Déclaration de conflit d'intérêts

A.G.-P. is a shareholder of Biomedica Molecular Medicine SL.

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Auteurs

Fernando Laso-García (F)

Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Centre, Neurology and Cerebrovascular Disease Group, Neuroscience Area Hospital La Paz Institute for Health Research - IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), Madrid, Spain.
PhD Program in Neuroscience, Autónoma de Madrid University-Cajal Institute, Madrid 28029, Spain.

Laura Casado-Fernández (L)

Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Centre, Neurology and Cerebrovascular Disease Group, Neuroscience Area Hospital La Paz Institute for Health Research - IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), Madrid, Spain.

Dolores Piniella (D)

Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Centre, Neurology and Cerebrovascular Disease Group, Neuroscience Area Hospital La Paz Institute for Health Research - IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), Madrid, Spain.
Universidad Autónoma de Madrid and IdiPAZ Health Research Institute, La Paz University Hospital, Madrid, Spain.

Mari Carmen Gómez-de Frutos (MC)

Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Centre, Neurology and Cerebrovascular Disease Group, Neuroscience Area Hospital La Paz Institute for Health Research - IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), Madrid, Spain.

Jone Karmele Arizaga-Echebarria (JK)

Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Centre, Neurology and Cerebrovascular Disease Group, Neuroscience Area Hospital La Paz Institute for Health Research - IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), Madrid, Spain.

María Pérez-Mato (M)

Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Centre, Neurology and Cerebrovascular Disease Group, Neuroscience Area Hospital La Paz Institute for Health Research - IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), Madrid, Spain.

Elisa Alonso-López (E)

Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Centre, Neurology and Cerebrovascular Disease Group, Neuroscience Area Hospital La Paz Institute for Health Research - IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), Madrid, Spain.

Laura Otero-Ortega (L)

Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Centre, Neurology and Cerebrovascular Disease Group, Neuroscience Area Hospital La Paz Institute for Health Research - IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), Madrid, Spain.

Susana Belén Bravo (SB)

Proteomic Unit, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.

María Del Pilar Chantada-Vázquez (MDP)

Proteomic Unit, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.

José Avendaño-Ortiz (J)

TumorImmunology Laboratory and Innate Immune Response Group, IdiPAZ Health Research Institute, Madrid, Spain.

Eduardo López-Collazo (E)

TumorImmunology Laboratory and Innate Immune Response Group, IdiPAZ Health Research Institute, Madrid, Spain.

María Isabel Lumbreras-Herrera (MI)

Molecular Oncology and Pathology Lab, Institute of Medical and Molecular Genetics-INGEMM, La Paz University Hospital-IdiPAZ, Madrid, Spain.

Angelo Gámez-Pozo (A)

Molecular Oncology and Pathology Lab, Institute of Medical and Molecular Genetics-INGEMM, La Paz University Hospital-IdiPAZ, Madrid, Spain.

Blanca Fuentes (B)

Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Centre, Neurology and Cerebrovascular Disease Group, Neuroscience Area Hospital La Paz Institute for Health Research - IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), Madrid, Spain.

Exuperio Díez-Tejedor (E)

Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Centre, Neurology and Cerebrovascular Disease Group, Neuroscience Area Hospital La Paz Institute for Health Research - IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), Madrid, Spain.

María Gutiérrez-Fernández (M)

Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Centre, Neurology and Cerebrovascular Disease Group, Neuroscience Area Hospital La Paz Institute for Health Research - IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), Madrid, Spain.

María Alonso de Leciñana (M)

Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Centre, Neurology and Cerebrovascular Disease Group, Neuroscience Area Hospital La Paz Institute for Health Research - IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), Madrid, Spain.

Classifications MeSH