Bone marrow mesenchymal stromal cell-derived small extracellular vesicles: A novel therapeutic agent in ischemic heart diseases

Abstract

Myocardial injury is a major pathological factor that causes death in patients with heart diseases. In recent years, mesenchymal stromal cells (MSCs) have been generally used in treating many diseases in animal models and clinical trials. mesenchymal stromal cells have the ability to differentiate into osteocytes, adipocytes and chondrocytes. Thus, these cells are considered suitable for cardiac injury repair. However, mechanistic studies have shown that the secretomes of mesenchymal stromal cells, mainly small extracellular vesicles (sEVs), have better therapeutic effects than mesenchymal stromal cells themselves. In addition, small extracellular vesicles have easier quality control characteristics and better safety profiles. Therefore, mesenchymal stromal cell-small extracellular vesicles are emerging as novel therapeutic agents for damaged myocardial treatment. To date, many clinical trials and preclinical experimental results have demonstrated the beneficial effects of bone marrow-derived mesenchymal stromal cells (BMMSCs) and bone marrow-derived mesenchymal stromal cells-small extracellular vesicles on ischemic heart disease. However, the validation of therapeutic efficacy and the use of tissue engineering methods require an exacting scientific rigor and robustness. This review summarizes the current knowledge of bone marrow-derived mesenchymal stromal cells- or bone marrow-derived mesenchymal stromal cells-small extracellular vesicle-based therapy for cardiac injury and discusses critical scientific issues in the development of these therapeutic strategies.

Mechanisms and therapeutic strategies of extracellular vesicles in cardiovascular diseases

“…MSCs can differentiate into bone cells, fat cells, and chondrocytes, which are considered suitable for heart damage repair. Many studies have shown that the secretions of MSCs, mainly EVs, have better therapeutic effects than the MSCs themselves 199 . EVs allow for easier quality control and better biosecurity.…”

“…Many studies have shown that the secretions of MSCs, mainly EVs, have better therapeutic effects than the MSCs themselves. 199 EVs allow for easier quality control and better biosecurity. Therefore, MSC‐derived EVs are becoming a new therapeutic approach for treating CVDs.…”

Extracellular Vesicles for Myocardial Ischemia-Reperfusion Injury: Still a Long Way [Letter]

“…Additionally, it was observed that this combination resulted in a decrease in the development of microcirculation thrombi within the affected region, an improvement in endothelial barrier function, and an increase in microvascular density in the injured area. 4 However, in specific circumstances, EVs can play a role in the mechanism of cardiovascular diseases (CVDs). 5 Serum EVs, for instance, play a part in the progression of pulmonary arterial hypertension and vascular calcification.…”

Decreased in n‐3 DHA enriched triacylglycerol in small extracellular vesicles of diabetic patients with cardiac dysfunction

“…In recent years, many studies have shown that sEVs carry bioactive cargoes, including lipids, proteins, and nucleic acids, which mediate cell-cell communication and regulate biological functions in recipient cells. 10,11 In diabetic condition, serum sEVs were shown to carry sonic hedgehog, a protein that modulates immunity, or arginase1 to induce endothelial dysfunction. 12 In addition, numbers of noncoding RNA are shown to carry by sEVs and are associated with incidence of diabetic complications.…”

“…However, some EVs are produced by direct budding from the plasma membrane, which also has size of 50–200 nm, and they cannot be distinguished by current isolation methods, 9 so the term of sEVs represents vesicles (50–200 nm) that are generated by both pathways. In recent years, many studies have shown that sEVs carry bioactive cargoes, including lipids, proteins, and nucleic acids, which mediate cell–cell communication and regulate biological functions in recipient cells 10,11 . In diabetic condition, serum sEVs were shown to carry sonic hedgehog, a protein that modulates immunity, or arginase1 to induce endothelial dysfunction 12 .…”