UFCC for Cardiovascular Cell Therapy Research Network

UFCC 心血管细胞治疗研究网络

• 批准号: 7747953
• 负责人: Carl J Pepine
• 金额: $ 54.65万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7747953
• 关键词: Acute; Acute myocardial infarction; Address; Adverse event; Animal Model; Area; Autologous; Award; Basic Science; Biological Availability; Blood Vessels; Bone Marrow Transplantation; CD34 gene; Cardiac; Cardiovascular Diseases; Cardiovascular system; Castor; Catheters; Cell Count; Cell Therapy; Cell Transplants; Cell physiology; Cells; Cessation of life; Chronic; Cicatrix; Clinic; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Collaborations; Committee Members; Communities; Community Practice; Contracts; Coronary; Data; Data Collection; Decision Making; Development; Development Plans; Diabetes Mellitus; Dose; Double-Blind Method; Educational workshop; Enrollment; Ensure; Epidemic; Ethnic Origin; Europe; Feasibility Studies; Florida; Fostering; Foundations; Functional disorder; Gases; Good Clinical Practice; Grant; Guidelines; Heart; Heart Diseases; Heart Transplantation; Heart failure; Hispanics; Histologic; Hypoxia; Image; Implant; Incidence; Incubated; Individual; Industry; Infarction; Injection of therapeutic agent; Institutional National Research Service Award; Investigation; Label; Lead; Left Ventricular Dysfunction; Letters; Literature; Location; Measures; Medical; Metabolic syndrome; Methods; Modeling; Morbidity - disease rate; Motion; Muscle Cells; Myocardial; Myocardial Ischemia; Myocardium; National Heart, Lung, and Blood Institute; Office for Protection from Research Risks; Outcome; Patient Care; Patient Recruitments; Patients; Perfusion; Phase; Phenotype; Physicians; Policies; Prevalence; Prevention; Principal Investigator; Private Practice; Procedures; Process; Prophylactic treatment; Protocols documentation; Publications; Puerto Rico; Randomized; Reaction; Records; Recruitment Activity; Regenerative Medicine; Reporting; Research; Research Design; Research Personnel; Resources; Review Committee; Risk; Role; Science; Side; Site; Site Visit; Skeletal Myoblasts; Staging; Stem cells; Structure; Technical Expertise; Techniques; Technology; Testing; Therapeutic; Therapeutic Intervention; Therapeutic Studies; Time; Training; Training Programs; Translating; Translations; Transplantation; Trauma; U-Series Cooperative Agreements; United States National Institutes of Health; Universities; Ventricular Function; Work; abstracting; aging population; base; capitate bone; cell type; cost; design; diabetic; diabetic patient; disability; follow-up; human subject; implantation; improved; innovation; insight; knowledge base; meetings; member; mortality; novel; novel strategies; pre-clinical; pre-clinical research; premature; programs; protocol development; quality assurance; research clinical testing; skills; stem cell biology; symposium; working group

DESCRIPTION (provided by applicant): 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. (End of Abstract)

描述（由申请人提供）： 该应用的长期目标是为心血管细胞治疗研究网络（CCTRN）建立佛罗里达大学临床中心（UFCC）。心血管（CV）细胞疗法是替代非承包心肌及其血管的令人兴奋的概念。但是，尽管大量的临床前和可行性临床研究能够转化这些发现以改善患者预后。为了满足这一需求，UFCC利用了干细胞生物学，再生医学，骨髓移植临床中心（NIH临床研究网络的一部分），新型成像资源，心脏移植程序和CV临床试验计划的既定UF计划。我们在多中心NHLBI和其他试验中成功合作的记录很长，有记录，以测试改善心脏灌注或功能并评估临床结果的策略。 我们的中心建议增强祖细胞功能将改善心力衰竭的CAD患者的心脏功能，并最终导致临床结果改善。这两种UFCC方案建议使用经皮导管直接壁内植入术，为左心室功能障碍/心力衰竭的CAD患者开发细胞疗法。这些第一个解决了糖尿病患者的祖细胞功能的增强。该假设是，在CD34+细胞中没有提高任何生物利用度将增强其固有的改善心肌功能的能力。特定目的测试是否增加CD34+细胞数量；内源性不给CD34+细胞施用；并在毛cd34+细胞中孵育和/或缺氧条件可改善壁运动或灌注异常。第二个方案中的假设是，等待心脏移植的患者为研究细胞治疗对功能的影响提供了独特的机会。具体目的测试是否骨骼成肌细胞（SKM）对心室功能的影响是否取决于细胞的存在，而不是对植入过程的反应。我们将确定在3个月时接受治疗和疾病的患者中是否存在更多的幸存细胞，并将使用与协议1优化的CD34+细胞共同管理的SKM仪来测量细胞疗法的影响。 由于这些研究将在等待移植的患者中进行，因此对外植的心脏和标记细胞的研究应产生有关细胞植入物的命运和特定位置的新信息。这两种方案的新特征是，这些细胞将在协议2中研究的外植型心脏中的细胞类型中进行无创和组织学的标记和验证。UFCC的其他独特方面包括训练核心，利用训练核心利用通过我们的K30和T32在相关领域中获得的结构以及与波尔特大学的相关领域和协作的结构。这项工作将提高我们对细胞疗法在CAD和心力衰竭患者中的​​作用的理解。 （抽象的结尾）