Microvesicle-mediated tissue regeneration mitigates the effects of cellular ageing

Panagiotou, N. , McGuinness, D., Jaminon, A. M.G., Mees, B., Selman, C. , Schurgers, L. and Shiels, P. G. (2023) Microvesicle-mediated tissue regeneration mitigates the effects of cellular ageing. Cells, 12(13), 1707. (doi: 10.3390/cells12131707) (PMID:37443741) (PMCID:PMC10340655)

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Abstract

Extracellular vesicles (EVs), comprising microvesicles (MVs) and exosomes (Exos), are membranous vesicles secreted by cells which mediate the repair of cellular and tissue damage via paracrine mechanisms. The action of EVs under normative and morbid conditions in the context of ageing remains largely unexplored. We demonstrate that MVs, but not Exos, from Pathfinder cells (PCs), a putative stem cell regulatory cell type, enhance the repair of human dermal fibroblast (HDF) and mesenchymal stem cell (MSC) co-cultures, following both mechanical and genotoxic stress. Critically, this effect was found to be both cellular age and stress specific. Notably, MV treatment was unable to repair mechanical injury in older co-cultures but remained therapeutic following genotoxic stress. These observations were further confirmed in human dermal fibroblast (HDF) and vascular smooth muscle cell (VSMC) co-cultures of increasing cellular age. In a model of comorbidity comprising co-cultures of HDFs and highly senescent abdominal aortic aneurysm (AAA) VSMCs, MV administration appeared to be senotherapeutic, following both mechanical and genotoxic stress. Our data provide insights into EVs and the specific roles they play during tissue repair and ageing. These data will potentiate the development of novel cell-free therapeutic interventions capable of attenuating age-associated morbidities and avoiding undesired effects.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McGuinness, Dr Dagmara and Selman, Professor Colin and Panagiotou, Dr Nikolaos and Shiels, Professor Paul
Authors: Panagiotou, N., McGuinness, D., Jaminon, A. M.G., Mees, B., Selman, C., Schurgers, L., and Shiels, P. G.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
College of Science and Engineering > School of Chemistry
Journal Name:Cells
Publisher:MDPI
ISSN:2073-4409
ISSN (Online):2073-4409
Published Online:23 June 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Cells 12(13): 1707
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
171868The basis of agonist and antagonist function at Free Fatty Acid receptor 2Graeme MilliganBiotechnology and Biological Sciences Research Council (BBSRC)BB/J013854/1MCSB - Molecular Pharmacology