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Review
. 2018 Jul 6;123(2):188-204.
doi: 10.1161/CIRCRESAHA.117.311215.

Extracellular Vesicles and the Application of System Biology and Computational Modeling in Cardiac Repair

Venkata Naga Srikanth Garikipati  1 , Farnaz Shoja-Taheri  2   3   4 , Michael E Davis  2   3   4 , Raj Kishore  5   6
Affiliations
Review

Extracellular Vesicles and the Application of System Biology and Computational Modeling in Cardiac Repair

Venkata Naga Srikanth Garikipati et al. Circ Res. .

Abstract

Recent literature suggests that extracellular vesicles (EVs), secreted from most cells and containing cell-specific cargo of proteins, lipids, and nucleic acids, are major driver of intracellular communication in normal physiology and pathological conditions. The recent evidence on stem/progenitor cell EVs as potential therapeutic modality mimicking their parental cell function is exciting because EVs could possibly be used as a surrogate for the stem cell-based therapy, and this regimen may overcome certain roadblocks identified with the use of stem/progenitor cell themselves. This review provides a comprehensive update on our understanding on the role of EVs in cardiac repair and emphasizes the applications of stem/progenitor cell-derived EVs as therapeutics and discusses the current challenges associated with the EV therapy.

Keywords: biology; exosomes; extracellular vesicles; lipids; stem cells.

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Figures

Fig-1:
Fig-1:. Exosome biogenesis:
Inward budding of membrane forms early endosome, which further results in accumulation of intraluminal vesicles (ILVs) consisting of cytoplasmic molecules such as proteins, lipids and nucleic acids within large multi vesicular bodies. Conversely, microvesicles and apoptotic bodies are formed by the outward budding of the plasma membrane. Both exosomes and microvesicles carry proteins, lipids and nucleic acids and transfer to recipient cells either by receptor ligand mediated transfer or directing fusing with the plasma membrane or through endocytosis.
Fig-2:
Fig-2:. EVs cargo of different cardiac cells and different stem/progenitor cells:
(A) cardiac cells including fibroblasts, macrophages, cardiomyocytes and endothelial cells EV cargo enriched with RNA/proteins etc.; (B) stem/progenitor cells including endothelial progenitor cells, mesenchymal stem cells, cardiac stem/progenitor cells, induced pluripotent stem cells and embryonic stem cells EV cargo enriched with RNA/proteins etc.
Fig-3:
Fig-3:. Stem/progenitor cells EVs communication with different cardiac cells in the injured heart:
Stem progenitor cells secreted exosomes transfer RNA and proteins to recipient cardiac cells (cardiomyocytes, fibroblasts, endothelial cells and macrophages) to repair the injured heart.
Fig-4:
Fig-4:. Mode of EVs action in vivo:
(A)To visualize specific expression of EV associated mRNA, Cre mRNA labelled with fluorescent or enzymatic reporter gene in EVs leads to excision of loxP sites in recipient cells in vivo, can be detected by fluorescence or colorimetry.(B) Florescence protein (GFP) reporters labelled EVs mRNA can be visualized and tracked in the recipient cells in vivo using florescence imaging.(C) Fluorescence protein (EGFP) and tandem dimer Tomato (tdTomato) reporters fused with a palmitoylation sequence for EV membrane labeling to visualize and track EVs uptake by recipient cells in vivo, can be detected by bioluminescent imaging. (D) EVs can be tracked by labelling EVs with iron-oxide nanoparticles and can be imaged using Magnetic resonance imaging. (E) EVs can be tracked by labelling EVs with radioisotopes and can be imaged using nuclear imaging.
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