Biomedical engineering education and research is an important mission of the GW School of Engineering and Applied Science (SEAS). Faculty and students in the Department of Biomedical Engineering (BME) work together to explore solutions to a number of pressing challenges, such as: improving cancer detection rates; developing medical diagnostic devices for more timely, personalized healthcare; spurring discoveries in tissue engineering and wound healing; and improving surgical outcomes.
The Efimov laboratory, headed by Prof. Igor Efimov, was established in 1994 and has over 20 years’ experience in the fields of cardiovascular engineering, cardiac electrophysiology and arrhythmia, biophotonics, and medical devices. The laboratory has been funded by NIH without interruption since 1998. During these years Prof. Efimov and his trainees have developed, improved, and applied a number of experimental methodologies based on biophotonic imaging to study normal and abnormal excitation of the heart. His principal interest is to improve our understanding of the development and function of the cardiovascular system, and to develop novel diagnostics and electrotherapies for cardiovascular diseases.
Another area of interest of this laboratory is applied physiology of the human heart. Since 2007, our laboratory has conducted research on the mechanisms of arrhythmogenic remodeling of the human heart during failure. In collaboration with clinicians, our laboratory has developed a program focused on human heart physiology. We have acquired and studied ex vivo more than 400 live human hearts, initially at Washington University in St. Louis and now at the George Washington University in Washington, DC. Our current Washington, DC regional partners are Washington Regional Transplant Community and Inova Fairfax Hospital. In our studies published in more than 50 peer-reviewed manuscripts, we present findings from donor hearts rejected for transplantation compared with hearts from end stage heart failure patients removed during transplantation. Based on these findings we aim to develop novel diagnostic and therapeutic approaches to treat heart failure and manage associated complications, including sudden death due to arrhythmia. Recently, we have developed an organotypic human slice preparation, which allows us to test the efficacy and safety of various biological and pharmacological therapies in human tissue, including novel pharmacological, reprogramming and gene editing therapies.
Translation of novel therapies from bench to bedside is hampered by profound disparities between animal and human genetics and physiology. The ability to test for efficacy and cardiotoxicity in a clinically relevant human model system would enable more rapid therapy development. We have developed a preclinical platform for validation of new therapies in human heart tissue using organotypic slices isolated from donor and end-stage failing hearts. A major advantage of the slices when compared with human iPS-derived cardiomyocytes is that native tissue architecture and extracellular matrix are preserved, thereby allowing investigation of multi-cellular physiology in normal or diseased myocardium. To validate this model, we used optical mapping of transmembrane potential and calcium transients. We found that normal human electrophysiology is preserved in slice preparations when compared with intact hearts, including slices obtained from the region of the sinus node. Physiology is maintained in slices during culture, enabling testing the acute and chronic effects of pharmacological, gene, cell, optogenetic, device, and other therapies. This methodology offers a powerful high-throughput platform for assessing the physiological response of the human heart to disease and novel putative therapies.
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