Therapeutic potentials of stem cell–derived exosomes in cardiovascular diseases

Abstract

Exosomes are extracellular vesicles released by many cell types with varying compositions. Major bioactive factors present in exosomes are protein, lipid, mRNA, and miRNA. Exosomes are fundamental regulators of cellular trafficking and signaling in both physiological and pathological conditions. Various conditions such as oxidative stress, endoplasmic reticulum stress, ribosomal stress, and thermal stress alter the concentration of exosomal mRNA, and miRNA, lipids, and proteins. Stem cell–derived exosomes have been shown to regulate a variety of stresses, either inhibiting or promoting cell balance. Stem cell–derived exosomes direct the crosstalk between various cell types which helps recovery by transferring information in proteins, lipids, and so on. This is one of the reasons why exosomes are used as biomarkers for a multitude of disease conditions. This review highlights the bioengineering of fabricated exosomal cargoes. It includes the manipulation and delivery of specific exosomal cargoes such as noncoding RNAs, recombinant proteins, immune modulators, therapeutic drugs, and small molecules. Such therapeutic approaches may precisely deliver the therapeutic drugs at the target site in the management of various disease conditions. Importantly, we have focused on the therapeutic applications of stem cell–derived exosomes in cardiovascular disease conditions such as myocardial infarction, ischemic heart disease, cardiomyopathy, heart failure, sepsis, and cardiac fibrosis. Generally, two approaches are being followed by researchers for exosomal bioengineering. This literature review will shed light on the role of stem cell–derived exosomes in stress balance and provides a new avenue for the treatment of cardiovascular diseases.

Stem Cell Therapy against Ischemic Heart Disease

“…The observed stem-cell-mediated benefits have been shown to be attributable to the paracrine functions of stem cells. In this aspect, exosomes appear to play a key role, particularly because of their contents of microRNAs, which have been found to be of great clinical potential in the treatment of ischemic heart disease [118,144,[191][192][193]. Taking into account the limited availability of autologous stem cells, exosomes from their allogeneic and xenogeneic counterparts may also offer significant therapeutic advantages [104].…”

Understanding molecular characteristics of extracellular vesicles derived from different types of mesenchymal stem cells for therapeutic translation

“…An analysis of the targeted organs shows that MSC-EVs are mostly studied for diseases originating in or affecting nerves, lung, brain, kidney, blood vessels, heart, pancreas, skin, bone, joint, liver and spine. As MSC-derived EV have been recognized as important in recent years, many review articles have well summarized therapeutic effects of MSC-EV in various diseases, including autoimmune diseases, 161 – 163 cancer, 164 cardiovascular disease, 165 , 166 diabetes, 167 , 168 fibrosis, 169 inflammation, 170 – 172 degenerative disease, 173 and injury. 174 Other articles reviewed clinical potential of MSC-EV targeting different organs, such as bone, 175 brain, 176 joint, 177 kidney, 178 – 181 liver, 182 lung, 183 – 186 nervous system, 187 skin, 188 spine, 189 heart, 190 and vascular system.…”

Mesenchymal stem cells with p38 mitogen-activated protein kinase interference ameliorate mouse ischemic stroke

“…Yingying Bai 1 , Lishan Wang 2 , Rong Xu 1 and Ying Cui 1 next to the injured environment. 3 After the in vitro labeling of MSC exosomes, we dynamically monitored the homing process of exosomes to the cerebral infarction site in vivo and observed their neuroprotective effects. 4 However, the application of MSCs is complicated by certain donor factors, such as old age and underlying diseases.…”

“…In addition to homing to the injury site, MSCs can not only differentiate into neurons, glial cells, and endothelial cells but also promote the repair of neurological damage through the secretion of trophic factors by exosomes next to the injured environment. 3 After the in vitro labeling of MSC exosomes, we dynamically monitored the homing process of exosomes to the cerebral infarction site in vivo and observed their neuroprotective effects. 4 However, the application of MSCs is complicated by certain donor factors, such as old age and underlying diseases.…”