Extracellular vesicles purified from serum-converted human platelet lysates offer strong protection after cardiac ischaemia/reperfusion injury

Dora Livkisa, Tzu Hsin Chang, Thierry Burnouf, Andreas Czosseck, Nhi Thao Ngoc Le, Gleb Shamrin, Wei Ting Yeh, Masao Kamimura, David J. Lundy

Research output: Contribution to journalArticlepeer-review

Abstract

Extracellular vesicles (EVs) from cultured cells or bodily fluids have been demonstrated to show therapeutic value following myocardial infarction. However, challenges in donor variation, EV generation and isolation methods, and material availability have hindered their therapeutic use. Here, we show that human clinical-grade platelet concentrates from a blood establishment can be used to rapidly generate high concentrations of high purity EVs from sero-converted platelet lysate (SCPL-EVs) with minimal processing, using size-exclusion chromatography. Processing removed serum carrier proteins, coagulation factors and complement proteins from the original platelet lysate and the resultant SCPL-EVs carried a range of trophic factors and multiple recognised cardioprotective miRNAs. As such, SCPL-EVs protected rodent and human cardiomyocytes from hypoxia/re-oxygenation injury and stimulated angiogenesis of human cardiac microvessel endothelial cells. In a mouse model of myocardial infarction with reperfusion, SCPL-EV delivery using echo-guided intracavitary percutaneous injection produced large improvements in cardiac function, reduced scar formation and promoted angiogenesis. Since platelet-based biomaterials are already widely used clinically, we believe that this therapy could be rapidly suitable for a human clinical trial.

Original languageEnglish
Article number122502
JournalBiomaterials
Volume306
DOIs
Publication statusPublished - Apr 2024

Keywords

  • Biodistribution
  • Bioprocessing
  • Extracellular vesicle
  • Myocardial infarction
  • Nanocarrier
  • Platelet

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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