The identification, characterization, and robust demonstrations of the ability of cultures of human derived cardiac progenitor cells (CPCs) to restore both contractile and vascular function in animal models underscores the enormous possibilities that would be created by exploiting this newly discovered biology of cardiac regeneration for therapeutic purposes. The translation of these fundamental discoveries into specific therapies that reduce morbidity and or mortality will require vigorous clinical data to demonstrate both safety and effectiveness. The objectives for this Cardiac Translational Research Implementation Program (C-TRIP) (P20) planning grant is to establish a multidisciplinary investigative team and develop methods for the subsequent execution of a clinical trial to test the hypothesis that CPCs can be employed to improve the recovery of ventricular performance and clinical outcomes of patients with the most advanced ischemic cardiomyopathy requiring a ventricular assist device (VAD) to sustain life. To meet these broad objectives, we propose to conduct clinical and experimental studies during the planning phase (Stage 1) that will position our team to perform a pivotal proof-of-concept clinical trial of CPCs in patients with ischemic cardiomyopathy supported on a VAD in Stage 2. We will establish whether biopsy samples from these patients with end stage heart failure have adequate numbers of quality CPCs for potential allograft use. Concurrently, we will use a canine model of chronic ischemic cardiomyopathy to study the durability of allograft CPCs comparing ventricular function, myocardial blood flow and metabolism with use of CPCs and preparations with augmented concentrations of the newly discovered vascular progenitor cells (VPCs). In Stage I we will also perform complimentary non invasive imaging assessments of cardiac performance in patients on a VAD to establish a baseline for a Stage 2 clinical trial of CPCs. Our immediate objective is to establish a cohesive multidisciplinary team to integrate the information generated in Stage I to improve the design and conduct of a pivotal proof of principle randomized, placebo-controlled clinical trial in Stage 2. The ascertainment of the therapeutic potential of autologous CPCs will require concerted fundamental and clinical investigations. We focus on patients with end stage ischemic cardiomyopathy supported by a VAD as an initial clinical step to attempt to harness the novel biology of cardiac regeneration of the expanding population with refractory heart failure despite conventional medications and devices.
In patients with advanced heart failure, there is increasing use of VAD as destination therapy for those not considered candidates for cardiac transplantation. Our investigative program will examine whether use of their autologous cardiac progenitor cells can favorably impact cardiac performance and their clinical outcomes while they are being supported by a VAD as a beginning step in the therapeutic use of cardiac regenerative biology.
| Gupta, Deepak K; Skali, Hicham; Rivero, Jose et al. (2014) Assessment of myocardial viability and left ventricular function in patients supported by a left ventricular assist device. J Heart Lung Transplant 33:372-81 |
| Welt, Frederick G P; Gallegos, Robert; Connell, John et al. (2013) Effect of cardiac stem cells on left-ventricular remodeling in a canine model of chronic myocardial infarction. Circ Heart Fail 6:99-106 |
| D'Amario, Domenico; Fiorini, Claudia; Campbell, Patricia M et al. (2011) Functionally competent cardiac stem cells can be isolated from endomyocardial biopsies of patients with advanced cardiomyopathies. Circ Res 108:857-61 |
