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

Authors
  • Takov, Kaloyan1
  • He, Zhenhe1
  • Johnston, Harvey E.2
  • Timms, John F.2
  • Guillot, Pascale V.2
  • Yellon, Derek M.1
  • Davidson, Sean M.1
  • 1 University College London, 67 Chenies Mews, London, WC1E 6HX, UK , London (United Kingdom)
  • 2 University College London, London, UK , London (United Kingdom)
Type
Published Article
Journal
Basic Research in Cardiology
Publisher
Springer Berlin Heidelberg
Publication Date
Mar 07, 2020
Volume
115
Issue
3
Identifiers
DOI: 10.1007/s00395-020-0785-3
Source
Springer Nature
Keywords
License
Green

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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