Fernanda Mesquita, PhD, on Using LAMA2-Exosomes to Improve Cardiomyocyte Survival in Stroke

“This system is very simple, so I think it's very translational. We can use recombinant systems that are human-based, so the chances of rejection are very low.”

Among the serious consequences of stroke caused by acute myocardial infarction is the death of cardiomyocytes. When these cells die in this context, they cannot be renewed or restored by currently available therapeutic methods, leading to additional issues. As such, great unmet need remains in this area from a therapeutic perspective, and there is an interest in developing new methods of either restoring cardiomyocytes or preventing their death in the first place.

One such approach being pioneered in preclinical research by Fernanda Mesquita, PhD, a research associate at The Texas Heart Institute, and her colleagues, is the use of mesenchymal stromal cell (MSC)-derived exosomes that have been coated in laminin alpha 2 (LAMA2), a major component of the cardiac extracellular matrix, in order to increase their specificity for the cardiomyocytes. In an in vitro setting, these exosomes were tested on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) undergoing ischemia-reperfusion. hiPSC-CMs treated with the exosomes 2 hours before a 4-hour ischemia were compared to hiPSC-CMs that did not receive the treatment. Notably, the hiPSC-CMs that were treated with the LAMA2-exosomes showed evidence of having received a 2-fold protective effect in comparison to the control group. Furthermore, following 1.5 hours of reperfusion the treated hiPSC-CMs recovered more quickly than did the control hiPSC-CMs.

Mesquita presented these findings, which her team concluded hold promise for the improvement of CM survival in ischemic cardiovascular disease, at the American Heart Association’s (AHA) Scientific Sessions 2023, held November 10-13 in Philadelphia, Pennsylvania. At the conference, CGTLive™ sat down with Mesquita to learn more about her findings. She discussed the unmet needs that her team hopes to address with their findings, noting the prevalence of cardiovascular disease today, and went over the main implications of the data they presented.

REFERENCE
1. Mesquita F, King M, Mendez CH. Laminin Alpha 2 Increases the Protective Effect of Exosomes in Human IPSC-Derived Cardiomyocytes During Ischemia-Reperfusion. Presented at: AHA Scientific Sessions 2023; November 10-13; Philadelphia, Pennsylvania. Mo1065