The objectives of this application are three fold;renew the University of Florida (UF) Regional Clinical Center (UFRCC) for the Cardiovascular Cell Therapy Research Network (CCTRN);renew the successful Investigator Training Core;and apply for the Clinical Research Coordinator Skill Development Program. Cell therapy is an exciting concept for treatment of CV disease (CVD), but despite abundant preclinical and feasibility clinical studies the ability to translate findings to improve patient outcomes has lagged. To address this need, the UFRCC utilizes established programs in Stem Cell Biology/Regenerative Medicine (T32), Bone Marrow Transplant Center (part of NIH/NCI clinical research network), novel imaging resources, the CTSI, Advanced Heart Failure/ Transplant Program, and CV Clinical Trials Program. In addition to success in CCTRN-1, we have a long record of successful collaborations in multicenter NHLBI and other trials testing strategies to improve cardiac perfusion or function and evaluate clinical outcomes. For this renewal application, we propose that enhancing progenitor cell function will improve cardiac function and lead to better clinical outcomes. Our first protocol addresses enhancing progenitor cell homing after non-STEMI. Novel features include a method to enhance binding to selectins using fucosyltransferase and its substrate (ASC-101) to complete sialylated Lewis X formation. UFRCC investigators have shown that ASC-101 enhances vasculogenesis;it has received orphan drug status for bone marrow transplantation;and is manufactured at a UF GMP-compliant facility. The second protocol uses a novel cell population (CD34+) in high dose for CAD patients with heart failure (like FOCUS). Other novel features include: increasing Angl- 7 by exposure to a small molecule shown by UFRCC investigators to enhance cell migration and vasculogenesis;a new delivery catheter (BioCardia, Helical);and cell selection method (Miltenyi Biotec). Additional unique aspects of the UFRCC include collaborations with University of Puerto Rico, and industry. This work will improve our understanding of the role of cell therapy in CVD patients.
This is an application for a regional center to continue a collaborative network that will evaluate novel cardiovascular cellular therapies targeting our leading cause of death and major cause of disability. Two phase 1 clinical trials are proposed to provide new knowledge about the clinical role of cell therapy for heart attack and heart failure.
|Taylor, Doris A; Perin, Emerson C; Willerson, James T et al. (2016) Identification of Bone Marrow Cell Subpopulations Associated With Improved Functional Outcomes in Patients With Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN Trial. Cell Transplant 25:1675-1687|
|Rocca, Domenico G Della; Willenberg, Bradley J; Qi, Yanfei et al. (2016) An injectable capillary-like microstructured alginate hydrogel improves left ventricular function after myocardial infarction in rats. Int J Cardiol 220:149-54|
|Bhatnagar, Aruni; Bolli, Roberto; Johnstone, Brian H et al. (2016) Bone marrow cell characteristics associated with patient profile and cardiac performance outcomes in the LateTIME-Cardiovascular Cell Therapy Research Network (CCTRN) trial. Am Heart J 179:142-50|
|Park, Ki; Lai, Dejian; Handberg, Eileen M et al. (2016) Association between High Endocardial Unipolar Voltage and Improved Left Ventricular Function in Patients with Ischemic Cardiomyopathy. Tex Heart Inst J 43:291-6|
|Stewart, Daniel C; Rubiano, AndrÃ©s; Santisteban, Monica M et al. (2016) Hypertension-linked mechanical changes of rat gut. Acta Biomater 45:296-302|
|Qi, Yan Fei; Zhang, Juan; Wang, Lei et al. (2016) Angiotensin-converting enzyme 2 inhibits high-mobility group box 1 and attenuates cardiac dysfunction post-myocardial ischemia. J Mol Med (Berl) 94:37-49|
|Rubiano, Andres; Qi, Yanfei; Guzzo, Dominic et al. (2016) Stem cell therapy restores viscoelastic properties of myocardium in rat model of hypertension. J Mech Behav Biomed Mater 59:71-7|
|Santisteban, Monica M; Kim, Seungbum; Pepine, Carl J et al. (2016) Brain-Gut-Bone Marrow Axis: Implications for Hypertension and Related Therapeutics. Circ Res 118:1327-36|
|Anderson, R David; Pepine, Carl J (2015) The Coronary Microcirculation in STEMI: The Next Frontier? Eur Heart J 36:3178-81|
|Qi, YanFei; Aranda, Juan M; Rodriguez, Vermali et al. (2015) Impact of antibiotics on arterial blood pressure in a patient with resistant hypertension - A case report. Int J Cardiol 201:157-8|
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