Human heart explant-derived extracellular vesicles: Characterization and effects on the in vitro recellularization of decellularized heart valves

Amanda Leitolis, Paula Hansen Suss, João Gabriel Roderjan, Addeli Bez Batti Angulski, Francisco Diniz Affonso da Costa, Marco Augusto Stimamiglio, Alejandro Correa

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Extracellular vesicles (EVs) are particles released from different cell types and represent key components of paracrine secretion. Accumulating evidence supports the beneficial effects of EVs for tissue regeneration. In this study, discarded human heart tissues were used to isolate human heart-derived extracellular vesicles (hH-EVs). We used nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) to physically characterize hH-EVs and mass spectrometry (MS) to profile the protein content in these particles. The MS analysis identified a total of 1248 proteins. Gene ontology (GO) enrichment analysis in hH-EVs revealed the proteins involved in processes, such as the regulation of cell death and response to wounding. The potential of hH-EVs to induce proliferation, adhesion, angiogenesis and wound healing was investigated in vitro. Our findings demonstrate that hH-EVs have the potential to induce proliferation and angiogenesis in endothelial cells, improve wound healing and reduce mesenchymal stem-cell adhesion. Last, we showed that hH-EVs were able to significantly promote mesenchymal stem-cell recellularization of decellularized porcine heart valve leaflets. Altogether our data confirmed that hH-EVs modulate cellular processes, shedding light on the potential of these particles for tissue regeneration and for scaffold recellularization.

Original languageEnglish (US)
Article number1279
JournalInternational journal of molecular sciences
Volume20
Issue number6
DOIs
StatePublished - Mar 2 2019
Externally publishedYes

Bibliographical note

Funding Information:
Funding: This study was supported by the National Health Fund, Brazilian Ministry of Health (Grant number 814611/2014) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil (CAPES)–Finance Code 001.

Keywords

  • Cardiac regions
  • Extracellular vesicle
  • Heart valve
  • Human heart
  • Mesenchymal stromal cells
  • Recellularization
  • Tissue engineering
  • Tissue explant

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