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Open Access 01-05-2020 | Original Contribution

Small extracellular vesicles secreted from human amniotic fluid mesenchymal stromal cells possess cardioprotective and promigratory potential

Authors: Kaloyan Takov, Zhenhe He, Harvey E. Johnston, John F. Timms, Pascale V. Guillot, Derek M. Yellon, Sean M. Davidson

Published in: Basic Research in Cardiology | Issue 3/2020

Abstract

Mesenchymal stromal cells (MSCs) exhibit antiapoptotic and proangiogenic functions in models of myocardial infarction which may be mediated by secreted small extracellular vesicles (sEVs). However, MSCs have frequently been harvested from aged or diseased patients, while the isolated sEVs often contain high levels of impurities. Here, we studied the cardioprotective and proangiogenic activities of size-exclusion chromatography-purified sEVs secreted from human foetal amniotic fluid stem cells (SS-hAFSCs), possessing superior functional potential to that of adult MSCs. We demonstrated for the first time that highly pure (up to 1.7 × 10¹⁰ particles/µg protein) and thoroughly characterised SS-hAFSC sEVs protect rat hearts from ischaemia–reperfusion injury in vivo when administered intravenously prior to reperfusion (38 ± 9% infarct size reduction, p < 0.05). SS-hAFSC sEVs did not protect isolated primary cardiomyocytes in models of simulated ischaemia–reperfusion injury in vitro, indicative of indirect cardioprotective effects. SS-hAFSC sEVs were not proangiogenic in vitro, although they markedly stimulated endothelial cell migration. Additionally, sEVs were entirely responsible for the promigratory effects of the medium conditioned by SS-hAFSC. Mechanistically, sEV-induced chemotaxis involved phosphatidylinositol 3-kinase (PI3K) signalling, as its pharmacological inhibition in treated endothelial cells reduced migration by 54 ± 7% (p < 0.001). Together, these data indicate that SS-hAFSC sEVs have multifactorial beneficial effects in a myocardial infarction setting.

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Title: Small extracellular vesicles secreted from human amniotic fluid mesenchymal stromal cells possess cardioprotective and promigratory potential
Authors: Kaloyan Takov
Zhenhe He
Harvey E. Johnston
John F. Timms
Pascale V. Guillot
Derek M. Yellon
Sean M. Davidson
Publication date: 01-05-2020
Publisher: Springer Berlin Heidelberg
Published in: Basic Research in Cardiology / Issue 3/2020
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-020-0785-3

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Small extracellular vesicles secreted from human amniotic fluid mesenchymal stromal cells possess cardioprotective and promigratory potential

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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