Exosomes: From Potential Culprits to New Therapeutic Promise in the Setting of Cardiac Fibrosis

Abstract

Fibrosis is a significant global health problem associated with many inflammatory and degenerative diseases affecting multiple organs, individually or simultaneously. Fibrosis develops when extracellular matrix (ECM) remodeling becomes excessive or uncontrolled and is associated with nearly all forms of heart disease. Cardiac fibroblasts and myofibroblasts are the main effectors of ECM deposition and scar formation. The heart is a complex multicellular organ, where the various resident cell types communicate between themselves and with cells of the blood and immune systems. Exosomes, which are small extracellular vesicles, (EVs), contribute to cell-to-cell communication and their pathophysiological relevance and therapeutic potential is emerging. Here, we will critically review the role of endogenous exosomes as possible fibrosis mediators and discuss the possibility of using stem cell-derived and/or engineered exosomes as anti-fibrotic agents.

Extracellular Vesicles as Therapeutic Agents for Cardiac Fibrosis

“…http://www.exocarta.org is referred to recently published reviews(Balbi et al, 2020;Tikhomirov et al, 2020).…”

Cell Sheet Comprised of Mesenchymal Stromal Cells Overexpressing Stem Cell Factor Promotes Epicardium Activation and Heart Function Improvement in a Rat Model of Myocardium Infarction

“…Accumulating data indicates an important role of extracellular vesicles (EVs) in the regulation of cell-to cell interaction, cell functions, and more importantly cardiac tissue protection [ 29 , 30 ]. We next evaluated the fraction of EVs that were secreted by SCF producing and unmodified MSCs.…”

“…Conventional interventions cannot resolve the problem of extensive irreversible loss of cardiomyocytes and tissue scarification while organ transplantation is still accessible only for a miniscule proportion of patients. A paradigm of using cells to promote the regeneration and replacement of damaged tissue was initially very attractive, Accumulating data indicates an important role of extracellular vesicles (EVs) in the regulation of cell-to cell interaction, cell functions, and more importantly cardiac tissue protection [29,30]. We next evaluated the fraction of EVs that were secreted by SCF producing and unmodified MSCs.…”

The Cellular Stress Response Interactome and Extracellular Matrix Cross-Talk during Fibrosis: A Stressed Extra-Matrix Affair

“…Immunostimulatory RNAs (like double stranded RNAs) generated through deregulated RNA processing pathways along with RNA binding proteins of RNA helicase (RNA sensors) family are emerging as important components of immune response pathways during sterile inflammation that involves DAMP sensing [15,16]. Mitochondrial quality control pathways intersecting with the endosomal compartments and lysosomes are recently reported to favor generation and release of mitochondrial-derived vesicles in former condition [143], further offering discernible biologically stable lipid vesicles that may help investigate how secreted cargos can impact tissue repair and homeostasis or trigger fibrosis, and can be extended to establishment of liquid biopsies for studying the progression of fibrotic diseases or alternatively these vesicles may serve as therapeutic tools like exosome-derived non coding RNAs [121,125,127,128,138,139,141,144] circulating microRNAs (miRNAs) and tissue resident miRNAs play paradoxical role both as anti-fibrotic [145][146][147][148] and profibrotic [149][150][151].…”