Abstract 15334: Laminin Alpha 2 Increases the Protective Effect of Exosomes in Human IPSC-Derived Cardiomyocytes During Ischemia-Reperfusion

Abstract

Acute myocardial infarction (AMI) is a leading cause of death and disability worldwide. With early treatment, restoration of blood flow to ischemic myocardium can be achieved and therefore reduce mortality risk. Evidence suggests that mesenchymal stromal cell (MSC)-derived exosomes (EXO) promote myocardial repair after AMI due to paracrine activity. Laminin alpha 2 (LAMA2) is a major cardiac extracellular matrix (ECM) component and can be used to produce cardiac-specific EXO. Here we coated MSC-derived EXOs in LAMA2 to enhance their recognition by human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We hypothesized that LAMA2-coated MSC-EXO would confer protective effects on CMs during ischemia-reperfusion. The LAMA2-EXO had a similar yield of particles, with a size range of 130nm as the control (gelatin-EXO). No cytotoxic effect was observed in CMs after 3-day exposure to LAMA2-EXO. CMs were then treated with LAMA2-EXO two hours prior to 4h ischemia (1% O 2 , 5% CO 2 , and glucose-free media). LAMA2-EXO had a 2-fold protective effect compared to non-treatment, and after 1.5h of reperfusion (5% CO 2 , CM-enriched media) CMs treated with LAMA2-EXO recovered faster than the control group. Conversely, due to the laminin 511/411 ECM component of endothelial cells (ECs), we did not see a significant protective effect nor a difference between LAMA2-EXO vs. the control in the EC ischemia-reperfusion group. This is the first report of suggesting the specificity of LAMA2-EXO to treat CM post-exposure to ischemia-reperfusion injury. Overall, these results indicate that LAMA2-EXO can be a promising treatment to target CM survival in ischemic cardiovascular disease.