The long-term objective of this application is to establish a University of Florida Clinical Center (UFCC) for the Cardiovascular Cell Therapy Research Network (CCTRN). Cardiovascular (CV) cell therapy is an exciting concept for replacement of noncontractile myocardium and its blood vessels. But despite abundant preclinical and feasibility clinical studies the ability to translate these findings to improve patient outcomes has lagged. To address this need, the UFCC utilizes established UF programs in Stem Cell Biology, Regenerative Medicine, Bone Marrow Transplant Clinical Center (part of the NIH clinical research network), novel imaging resources, the Heart Transplant Program and CV Clinical Trials Program. We have a long and well documented record of successful collaboration in multicenter NHLBI and other trials to test strategies to improve cardiac perfusion or function and evaluate clinical outcomes. Our center proposes that enhancing progenitor cell function will improve cardiac function in CAD patients with heart failure and ultimately lead to improved clinical outcomes. The two UFCC protocols propose to develop cell therapy for CAD patients with left ventricular dysfunction/heart failure using direct intramural implantation by percutaneous catheter. The first of these addresses enhancing progenitor cell function in diabetic patients. The hypothesis is in that improving NO bioavailability within the CD34+ cells will enhance their inherent ability to improve myocardial function.
Specific aims test whether increasing CD34+ cell numbers;endogenous NO administration to CD34+ cells;and incubating CD34+ cells under croyperserved and/or hypoxic conditions improves wall motion or perfusion abnormalities. The hypothesis in the second protocol is that patients awaiting cardiac transplantation provide a unique opportunity to investigate effects of cell therapy on function.
Specific aims test whether skeletal myoblasts'(SkM) effect on ventricular function will be dependent on the presence of cells and not a reaction to the implantation process. We will determine whether there are greater numbers of surviving cells among patients treated and redosed at 3 months and will measure the effects of cell therapy using SkM co-administered with CD34+ cells optimized in Protocol 1. Since these studies will be performed in patients awaiting transplantation, studies of explanted hearts and labeled cells should yield new information on the fate and specific location of cell implants. Novel features of both protocols are that the cells will be labeled and tracked noninvasively and verified histologically in terms of cell type in the explanted hearts investigated in Protocol 2. Other unique aspects of the UFCC include the Training Core utilizing the structure available through our K30 and T32 programs in related areas and collaborations with the University of Puerto Rico and industry. This work will improve our understanding of the role of cell therapy in patients with CAD and heart failure.
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