Extracellular vesicles from human cardiac fibroblasts modulate calcium cycling in human stem cell-derived cardiomyocytes
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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 Ca2+ 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 Ca2+ transients were analyzed. Fibroblast-secreted EVs abbreviate the Ca2+ 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 Ca2+ handling.
Date Acceptance
2022-03-23
Citation
Cells, 11 (7), pp.1171-1171
ISSN
2073-4409
Publisher
MDPI AG
Start Page
1171
End Page
1171
Journal / Book Title
Cells
Volume
11
Issue
7
Copyright Statement
© 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/
License URL
Sponsor
British Heart Foundation
Identifier
https://www.mdpi.com/2073-4409/11/7/1171
Grant Number
FS/16/76/32409
Subjects
calcium cycling
cardiomyocyte
chromatography
excitation-contraction coupling
extracellular vesicles
fibroblast
isolation
stem cell
ultrafiltration
Calcium
Extracellular Vesicles
Fibroblasts
Humans
Induced Pluripotent Stem Cells
Myocytes, Cardiac
Fibroblasts
Myocytes, Cardiac
Humans
Calcium
Induced Pluripotent Stem Cells
Extracellular Vesicles
Publication Status
Published online
Date Publish Online
2022-03-30