NSF/FDA SIR: 3D Human Stem Cell Cardiac Model for Cardiac Electrophysiology Medical Device Safety Assessment

University Of Maryland, College Park, College Park MD

Investigators

Abstract

Heart Failure (HF) is the leading cause of death worldwide. Recently, a new medical device therapy called Cardiac Contractility Modulation (CCM) has been approved by the Food and Drug Administration (FDA) to be used in eligible HF patients. CCM devices are implantable electrical pulse generators that deliver stimulations to the heart to increase the strength of the heart contraction during HF. The true benefit of these devices has not been reached due to a lack of predictive human-based preclinical test methods. The goal of this one-year NSF/FDA Scholar-in-Residence program is to develop a 3D Printed Human Heart Model to predict the effects of cardiac electrophysiology medical devices (e.g., CCM) at the bench. This model has a potential to reduce the burden on animal testing and clinical trials for cardiacmedical device development and may inform FDA regulatory review process and ultimately accelerate heart failure patients access to innovative, safe and effective devices. This study will partner faculty and students at the University of Maryland and regulatory scientists at the Center for Devices and Radiological Health (CDRH) at the FDA. The goals of this project are to develop a robust high-throughput 3D printed (3DP) engineered heart tissue (EHT) model composed of human induced pluripotent stem cell derived cardiomyocytes (hiPSC CMs) and to apply this model to preclinical assessment of human cardiac electrophysiology medical devices in vitro. Specifically, we will leverage our previous experience and development of a cell adhesion centrifugation (CAC) assay to investigate its utility for generating EHTs in a quantity sufficient to support high-throughput regulatory studies. This model will be used to elucidate the acute effects of Cardiac Contractility Modulation (CCM) therapy medical devices on human cardiac function in vitro. As such we will investigate the functional consequences of clinical CCM stimulation parameters on 3DP EHTs and quantify the response for all three cardiac excitation-contraction coupling readouts (i.e., electrophysiology, calcium handling, and contraction) in a high-throughput manner. The work described in this project will address current regulatory knowledge gaps and demonstrate the utility of hiPSC-CM 3DP EHT constructs to assess safety and effectiveness of cardiac electrophysiology medical devices in vitro. 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.