Abstract
Myocardial infarction (MI) is a devastating disease with high morbidity and mortality caused by the irreversible loss of functional cardiomyocytes and heart failure (HF) due to the restricted blood supply. Mesenchymal stem cells (MSCs) have been emerging as lead candidates to treat MI and subsequent HF mainly through secreting multitudinous factors of which exosomes act as the most effective constituent to boost the repair of heart function through carrying noncoding RNAs and proteins. Given the advantages of higher stability in the circulation, lower toxicity, and controllable transplantation dosage, exosomes have been described as a wonderful and promising cell-free treatment method in cardiovascular disease. Nowadays, MSC-derived exosomes have been proposed as a promising therapeutic approach to improve cardiac function and reverse heart remodeling. However, exosomes' lack of modification cannot result in desired therapeutic effect. Hence, optimized exosomes can be developed via various engineering methods such as pharmacological compound preconditioned MSCs, genetically modified MSCs, or miRNA-loaded exosomes and peptide tagged exosomes to improve the targeting and therapeutic effects of exosomes. The biological characteristics, therapeutic potential, and optimizing strategy of exosomes will be described in our review.
Highlights
Myocardial infarction (MI) is a devastating disease with high morbidity and mortality caused by the irreversible loss of functional cardiomyocytes due to the restricted blood supply
Mesenchymal stem cells (MSCs) have attracted wide attention due to their high reproductive activity, multilineage differentiation potential to mesoderm or nonmesoderm tissues, immunomodulatory properties, and broad-spectrum releasing of cytokines which endow themselves as a promising candidate to mitigate MI and subsequent heart failure (HF) [1, 2]
The low retention and poor cell survival rates in the myocardium hamper the therapeutic effects of MSC which explain that the repair mechanisms in cardiac function and structure mainly rely on the paracrine action of MSCs other than in situ differentiation into cardiomyocytes
Summary
Myocardial infarction (MI) is a devastating disease with high morbidity and mortality caused by the irreversible loss of functional cardiomyocytes due to the restricted blood supply. The low retention and poor cell survival rates in the myocardium hamper the therapeutic effects of MSC which explain that the repair mechanisms in cardiac function and structure mainly rely on the paracrine action of MSCs other than in situ differentiation into cardiomyocytes. The paracrine factors released from MSCs have been proved to possess the major regulation effect on myocardial regeneration and angiogenesis [7, 8] through promoting the proliferation of cardiomyocytes and endotheliocytes and restraining apoptosis of cardiomyocytes [9, 10]. Emerging lines of evidence have pointed out the powerful therapeutic effects of MSCs in the recovery of cardiac function similar to their parent MSCs mainly through secreting extracellular vesicles (EVs) such as exosomes, microvesicle (MV), and apoptotic body to transport multitudinous molecules from donor cells to recipient target cells [11,12,13]. This review is aimed at discussing the current knowledge on biological characteristics and the mechanisms of exosomes, the problems, and the optimization strategies of exosomes to improve therapeutic effect and disclose their huge therapeutic potential for MI treatment
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