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Microvesicle-Mediated Tissue Regeneration Mitigates the Effects of Cellular Ageing

View ORCID ProfileNikolaos Panagiotou, Dagmara McGuiness, Armand M.G. Jaminon, Barend Mees, Colin Selman, Leon Schurgers, Paul G. Shiels
doi: https://doi.org/10.1101/2022.04.13.488143
Nikolaos Panagiotou
1Wolfson Wohl Cancer Research Centre, College of Medical, Veterinary & Life Sciences, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK
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  • ORCID record for Nikolaos Panagiotou
Dagmara McGuiness
1Wolfson Wohl Cancer Research Centre, College of Medical, Veterinary & Life Sciences, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK
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Armand M.G. Jaminon
2Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
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Barend Mees
3Department of Vascular Surgery, Maastricht University Medical Centre (MUMC), Maastricht, the Netherlands
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Colin Selman
4Graham Kerr Building, College of Medical, Veterinary & Life Sciences, Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow G12 8QQ, UK
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Leon Schurgers
2Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
5Institute of Experimental Medicine and Systems Biology, RWTH University Hospital, Aachen, Germany
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Paul G. Shiels
1Wolfson Wohl Cancer Research Centre, College of Medical, Veterinary & Life Sciences, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK
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  • For correspondence: paul.shiels@glasgow.ac.uk
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ABSTRACT

An ageing global population brings with it a significant burden of age-related morbidities. Recently, a novel intervention strategy to mitigate this burden has emerged, involving the use of Extracellular Vesicles (EV), comprising use of Microvesicles (MV) and Exosomes (Exo). These membranous vesicles are secreted by cells and mediate repair of cellular and tissue damage via paracrine mechanisms, involving interaction of their bioactive cargoes with stem cells. The actions of EV under normative and morbid conditions in the context of ageing remains largely unexplored. We now show that MV, but not Exo, from Pathfinder cells (PC), 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 still remained therapeutic following genotoxic stress. These observations were further confirmed in HDF and Vascular Smooth Muscle Cell (VSMC) co-cultures of increasing cellular age. In a model of comorbidity, comprising co-cultures of HDF and highly senescent Abdominal Aortic Aneurysm (AAA) VSMC, MV administration appeared to be senolytic following both mechanical and genotoxic stress, prior to enabling regeneration. To our knowledge, this is the first description of EV-based senolysis. It provides novel insight into understanding the biology of EV and the specific roles they play during tissue repair and ageing. These data will potentiate development of novel cell-free therapeutic interventions capable of attenuating age-associated morbidities and avoiding undesired effects. Ultimately, this might act as a possible intervention strategy to extend human healthspan.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 13, 2022.
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Microvesicle-Mediated Tissue Regeneration Mitigates the Effects of Cellular Ageing
Nikolaos Panagiotou, Dagmara McGuiness, Armand M.G. Jaminon, Barend Mees, Colin Selman, Leon Schurgers, Paul G. Shiels
bioRxiv 2022.04.13.488143; doi: https://doi.org/10.1101/2022.04.13.488143
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Microvesicle-Mediated Tissue Regeneration Mitigates the Effects of Cellular Ageing
Nikolaos Panagiotou, Dagmara McGuiness, Armand M.G. Jaminon, Barend Mees, Colin Selman, Leon Schurgers, Paul G. Shiels
bioRxiv 2022.04.13.488143; doi: https://doi.org/10.1101/2022.04.13.488143

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