Hypoxia and TNF‐alpha modulate extracellular vesicle release from human induced pluripotent stem cell‐derived cardiomyocytes

• DOI: 10.1002/jev2.70000
• Publication Date: 2024-11-07T12:24:17Z
• Authors: Margarida Viola; Maarten P. Bebelman; Renee G. C. Maas; Willemijn S. de V...; Frederik J. Verweij; Cor S. Seinen; Saskia C. A. de J...; Pieter Vader; Dirk Michiel Pegtel; Joost Petrus Gera...
• Keywords: Extracellular Vesicles; Extracellular vesicles; Hypoxia; Alpha (finance)

Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in the heart under homeostatic and pathological conditions, such myocardial infarction (MI). However, basic mechanisms driving cardiomyocyte-derived EV (CM-EV) production following stress are poorly understood. In this study, we generated human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that express NanoLuc-tetraspanin reporters. These modified hiPSC-CMs allow for quantification tetraspanin-positive CM-EV secretion from small numbers cells without need time-consuming isolation techniques. We subjected these to a panel molecules study their effect on biogenesis basal stress-associated conditions. observed is context-dependent hiPSC-CMs. Nutrient starvation decreases while hypoxia increases CM-EVs nSmase2-dependent manner. Moreover, inflammatory cytokine TNF-α increased through process involving NLRP3 inflammasome activation mTOR signalling. Here, detailed first time regulatory upon MI-associated stressors.