Computer Simulations of MSC-Heart Muscle Interactions Identify A Family of MSCs that Produce Few Side Effects

A research team at the Icahn School of Medicine at Mount Sinai has utilized a mathematical modeling to simulate the delivery of human mesenchymal stem cells to a damaged heart. In doing so, they found that a particular subset of harvested MSCs minimizes the risks associated with this therapy. This study represents a development that could lead to novel strategies to repair and regenerate heart muscle and might even improve stem cell treatments for heart attack patients.

In the United States alone, one person suffers a myocardial infarction or heart attack every 43 seconds (on the average). The urgency of this situation has motivated stem cells scientists and cardiologists to develop novel therapies to repair and regenerate heart muscle. One of these therapies includes the implantation of human mesenchymal stem cells (hMSCs). However, in clinical trials the benefits of hMSC implantation have often been modest and even transient. This might reflect our understanding of the mechanism by which hMSCs influence cardiac function.

Kevin D. Costa and his colleagues at the Icahn School of Medicine have used mathematical modeling to simulate the electrical interactions between implanted hMSCs and endogenous heart cells. They hoped to eventually understand the possible adverse effects of hMSC transplantation and new methods for reducing some potential risks of this therapy.

Implanted hMSCs can disrupt the electrical connections between heart muscle cells and can even cause the heart to beat irregularly; a condition called “arrhythmias.” One particular type of hMSCs, however, did not express an ion channel called EAG1 (which stands for “ether-a-go-go”). The EAG1-less hMSCs did not cause arrhythmias at nearly the rate as the EAG1-containing hMSC, in computer simulations run by Costa’s group.

These EAG1-less hMSCs, also known as “Type C” MSCs, minimized electrochemical disturbances in cardiac single-cell and tissue-level electrical activity. The benefits of these EAG1-less hMSCs may enhance the safety of hMSC treatments in heart attack patients who receive stem cell therapy. This advance could therefore lead to new clinical trials and future improvements in treatment of patients with heart failure.

Costa’s study might provide a template for future computational studies on mesenchymal stem cells. It also provides novel insights into hMSC-heart cell interactions that can guide future experimental studies to understand the mechanisms that underlie hMSC therapy for the heart.

This work was published in Joshua Mayourian et al., “Modeling Electrophysiological Coupling and Fusion between Human Mesenchymal Stem Cells and Cardiomyocytes, PLOS Computational Biology, 2016; 12 (7): e1005014. DOI: 10.1371/journal.pcbi.1005014.