Mesenchymal Stem Cell-Derived Exosomes Improve the Microenvironment of Infarcted Myocardium Contributing to Angiogenesis and Anti-Inflammation

Abstract

Background/Aims: Bone marrow mesenchymal stem cells (MSCs) widely applied for treating myocardial infarction face survival challenges in the inflammatory and ischemia microenvironment of acute myocardial infarction. The study hypothesized that MSC-derived exosomes play a significant role in improving microenvironment after acute myocardial infarction and aimed to investigate the paracrine effects of exosomes on angiogenesis and anti-inflammatory activity. Methods: MSCs were cultured in DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin for 48 h. MSC-derived exosomes were isolated using ExoQuick-TC. Tube formation and T-cell proliferation assays were performed to assess the angiogenic potency of MSC-derived exosomes. Acute myocardial infarction was induced in Sprague-Dawley rats, and myocardium bordering the infarcted zone was injected at four different sites with phosphate-buffered saline (PBS, control), MSC-derived exosomes, and exosome-depleted MSC culture medium. Results: MSC-derived exosomes significantly enhanced the tube formation of human umbilical vein endothelial cells, impaired T-cell function by inhibiting cell proliferation in vitro, reduced infarct size, and preserved cardiac systolic and diastolic performance compared with PBS markedly enhancing the density of new functional capillary and hence blood flow recovery in rat myocardial infarction model. Conclusions: Exosomes stimulate neovascularization and restrain the inflammation response, thus improving heart function after ischemic injury.

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

“…Feng et al31 demonstrated that exosomes released from ischemic preconditioned MSCs contained an increased amount of miR‐22, which could exert a silence effect on methyl CpG binding protein 2 to ameliorate apoptosis in mice with AMI. Our group also proved that MSC‐derived exosomes could inhibit inflammation, augment vasculogenesis, and restore cardiac function in MI by activating and modifying the microRNA profiles of cardiac stem cells 32, 33. Despite these therapeutic effects of MSCs‐exosomes, targeting intended tissues or cells while avoiding nonintended delivery still remains challenging.…”

Cardiac Cell Therapies for the Treatment of Acute Myocardial Infarction: A Meta-Analysis from Mouse Studies

“…However, when highly conserved biological pathways and processes are targeted, we believe the mouse to be a valid model for the prediction of clinical results of regenerative therapy. Beneficial effects of cardiac cell therapies have been mainly attributed to modulation of apoptosis [28, 29], inflammation and angiogenesis [30-33]. Intriguingly, these mechanisms are highly conserved biological pathways in mammals [34-36].…”

Mesenchymal stem cells-derived exosomal microRNAs contribute to wound inflammation

“…Studies have shown that MSC-EXO significantly depressed lymphocyte proliferation, restrained the inflammatory response, and played a cardioprotective role. A decrease in the concentration of exosomes, results in the slower recovery of damaged hearts (Teng et al, 2015). Thus, further investigations are necessary to explain the transporter roles of MSC-EXO in wound healing and analyze the composition of exosomes to reveal their detailed mechanisms in chronic inflammation.…”