CAREER: Engineering Autonomic Control of Cardiac Tissues

The human heart is a critical organ that is responsible for pumping blood to the rest of the body. This pump is able to speed up or slow down to ensure enough blood is carried throughout our bodies during times of activity or during times of rest. The heart is able to achieve this variation in pumping rate through control by the nervous system. Neurons send signals to the heart to change the beat rate and help make sure the heart beats in unison. This Faculty Early Career Development (CAREER) project supports fundamental research to understand how neurons connect to the heart and improve heart function. This research will be achieved by using stem cells in three-dimensional engineered structures to examine how the neurons connect to the heart cells and how the electrical stimulus from the neurons improves beating heart function. Results will help advance knowledge of heart biology, will promote engineering solutions for potential future therapies, and can be used as a drug screening platform. This project is fully integrated with community outreach in the Southern Tier of NY. which is demonstrated through the development of biomedical engineering teaching modules for high school classrooms in local rural communities. The investigator’s long-term career goal is to become a scientific leader in the fields of stem cell and tissue engineering with a specific focus on cardiovascular tissue models and biomanufacturing. Towards this goal, the goal of this CAREER project is to interrogate the role of autonomic neural stimulation on the function of engineered cardiac tissues in vitro. A detailed understanding of the multicellular interactions that occur in the heart is a necessary, but challenging, aspect to improve the performance of engineered cardiac models. The research and education plan is organized under 3 separate objectives. The first objective is to engineer heterotypic multicellular models to measure the effects of autonomic innervation on cardiac contractile behavior and cellular composition. To achieve this, pluripotent stem cells will be differentiated into sympathetic and parasympathetic neurons. These neuronal cell populations will be mixed with cardiomyocytes at different developmental stages to investigate their influence over beat rate, contraction force, and calcium handling kinetics. The second objective is to develop a variable frequency electrical stimulation bioreactor to mimic the signals that the cardiomyocytes receive from the autonomic neurons. Cardiac tissues will be cultured under variable electrical stimulation and their contractile properties will be compared directly to innervated and non-innervated tissues to determine if variable electrical stimulation improves cardiac tissue responses to stress exposure. The third objective is to achieve research and educational integration through activities for high school students and undergraduate students incorporating tissue engineering, cardiovascular physiology, biomanufacturing, and stem cell biology. As part of the outreach efforts, a series of STEM based games will be developed and used as a centerpiece for community outreach in local, rural school districts. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.