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

doi:10.1016/j.biomaterials.2024.122502

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

Biomaterials. 2024 Apr:306:122502. doi: 10.1016/j.biomaterials.2024.122502. Epub 2024 Feb 6.

Authors

Dora Livkisa¹, Tzu-Hsin Chang², Thierry Burnouf³, Andreas Czosseck², Nhi Thao Ngoc Le¹, Gleb Shamrin⁴, Wei-Ting Yeh⁵, Masao Kamimura⁶, David J Lundy⁷

Affiliations

¹ International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
² Graduate Institute of Biomedical Materials & Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
³ International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Materials & Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; International Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: thierry@tmu.edu.tw.
⁴ Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
⁵ School of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
⁶ Department of Medical and Robotic Engineering Design, Faculty of Advanced Engineering, Tokyo University of Science, Japan.
⁷ International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Materials & Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; Center for Cell Therapy, Taipei Medical University Hospital, Taipei, Taiwan. Electronic address: dlundy@tmu.edu.tw.

PMID: 38354518
DOI: 10.1016/j.biomaterials.2024.122502

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.

Keywords: Biodistribution; Bioprocessing; Extracellular vesicle; Myocardial infarction; Nanocarrier; Platelet.

MeSH terms

Animals
Endothelial Cells / metabolism
Extracellular Vesicles* / metabolism
Humans
Mice
Myocardial Infarction*
Myocytes, Cardiac / metabolism
Reperfusion Injury* / metabolism