Extracellular Vesicles from Human Cardiac Fibroblasts Modulate Calcium Cycling in Human Stem Cell-Derived Cardiomyocytes

Cardiac fibroblasts regulate the development of the adult cardiomyocyte phenotype and cardiac remodeling in disease. We investigate the role that cardiac fibroblasts-secreted extracellular vesicles (EVs) have in the modulation of cardiomyocyte Ca cycling-a fundamental mechanism in cardiomyocyte func...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2022-03, Vol.11 (7), p.1171
Main Authors: Wang, Brian X, Nicastro, Laura, Couch, Liam, Kit-Anan, Worrapong, Downing, Barrett, MacLeod, Kenneth T, Terracciano, Cesare M
Format: Article
Language:English
Subjects:
Biobanks
Calcium (intracellular)
Calcium - metabolism
cardiomyocyte
Cardiomyocytes
CD63 antigen
CD81 antigen
CD9 antigen
Centrifugation
Chromatography
Coronary artery disease
Electron microscopy
Extracellular vesicles
Extracellular Vesicles - metabolism
fibroblast
Fibroblasts
Glass substrates
Heart diseases
Humans
Induced Pluripotent Stem Cells - metabolism
isolation
Metabolism
Myocytes, Cardiac - metabolism
Phenotypes
Plating
Pluripotency
stem cell
Stem cells
Ultrafiltration
Ventricle
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Summary:Cardiac fibroblasts regulate the development of the adult cardiomyocyte phenotype and cardiac remodeling in disease. We investigate the role that cardiac fibroblasts-secreted extracellular vesicles (EVs) have in the modulation of cardiomyocyte Ca cycling-a fundamental mechanism in cardiomyocyte function universally altered during disease. EVs collected from cultured human cardiac ventricular fibroblasts were purified by centrifugation, ultrafiltration and size-exclusion chromatography. The presence of EVs and EV markers were identified by dot blot analysis and electron microscopy. Fibroblast-conditioned media contains liposomal particles with a characteristic EV phenotype. EV markers CD9, CD63 and CD81 were highly expressed in chromatography fractions that elute earlier (Fractions 1-15), with most soluble contaminating proteins in the later fractions collected (Fractions 16-30). Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were treated with fibroblast-secreted EVs and intracellular Ca transients were analyzed. Fibroblast-secreted EVs abbreviate the Ca transient time to peak and time to 50% decay versus serum-free controls. Thus, EVs from human cardiac fibroblasts represent a novel mediator of human fibroblast-cardiomyocyte interaction, increasing the efficiency of hiPSC-CM Ca handling.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells11071171