Native and bioengineered extracellular vesicles for cardiovascular therapeutics

Abstract

Extracellular vesicles (EVs) are a heterogeneous group of natural particles with relevance for the treatment of cardiovascular diseases. The endogenous properties of these vesicles allow them to survive in the extracellular space, bypass biological barriers and deliver their biologically active molecular cargo to recipient cells. Moreover, EVs can be engineered to enhance their stability, bioactivity, presentation and capacity for on target binding at both cell type and tissue levels. The therapeutic potential of native (i.e., EVs that were not modified via donor cell or direct modulation) and engineered (i.e. EVs that were modified either pre-or post-isolation or whose pharmacokinetics/presentation was altered using engineering methodologies EVs is still limitedly explored in the context of cardiovascular diseases. Efforts to tap into the therapeutic potential of EVs will require innovative approaches and a comprehensive integration of knowledge gathered from decades of molecular compound delivery. In this review, we outline the endogenous properties of EVs that make them natural delivery agents as well as those features that can be improved using bioengineering approaches. We also discuss the therapeutic applications of native and engineered EVs for cardiovascular applications and examine the opportunities and challenges that need to be addressed to advance this research area with an emphasis on clinical translation. Key points• EVs secreted from stem/progenitor cells as well as differentiated somatic cells have regenerative properties in the context of myocardial infarction, ischemic limb, chronic wounds and stroke.

Improvement of sensory neuron growth and survival via negatively regulating PTEN by miR-21-5p-contained small extracellular vesicles from skin precursor-derived Schwann cells

“…In addition, other selected miRs showed unfavorable expression level in OGD-injured sensory neurons after SKP-SC-EV treatment, which indicate that the physicochemical properties and molecular-compound delivery of EVs are determined by their cell, tissue, or fluid of origin, and the heterogeneity present in the source is reflected in the composition of the EVs. Therefore, the properties can be harnessed by bioengineering, to improve their bioactivity, stability, targeting, and presentation of native EVs [57]. Furthermore, the testing of more candidate miRs derived from SKP-SCs is ongoing via high-throughput analysis, and should yield more useful information for the development of innovative cell-free therapy for nerve regenerative translational medicine from bench to bedside.…”

Importance of extracellular vesicles in hypertension

“…EVs are able to deliver multiple bioactive molecules that may or may not act synergistically, which allows the tailoring of the method of delivery to optimize their therapeutic effects 123. There are extensive studies reporting the use of EVs in cardiovascular diseases 16,124. In addition, the inhibition of exosome secretion not only has some physiological consequences,41 but also may have some effects to certain diseases.…”

Recent Development in Therapeutic Cardiac Patches

“…Instead of the direct interact of cells with host cardiomyocytes, paracrine factors released by cells play a key role in heart repair ( 102 ). Among these factors, growth factors (GFs), extracellular vesicles (EVs) and microRNAs are mostly studied ( 103 ). Different from cellular patches, acellular patches integrated with paracrine factors exhibit more direct therapeutic effects ( 104 ).…”