UFCC for Cardiovascular Cell Therapy Research Network

描述(由申请人提供)： 这项申请的长期目标是为心血管细胞治疗研究网络(CCTRN)建立一个佛罗里达大学临床中心(UFCC)。心血管细胞治疗是一种替代非收缩心肌及其血管的令人兴奋的概念。但是，尽管进行了大量的临床前研究和可行性临床研究，但将这些发现转化为改善患者预后的能力一直滞后。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)、新的成像资源、心脏移植计划和CV临床试验计划中的现有UF计划。我们在多中心NHLBI和其他试验中有成功合作的长期和良好的记录，以测试改善心脏灌注或功能的策略，并评估临床结果。 我们中心认为，增强祖细胞功能将改善合并心力衰竭的冠心病患者的心功能，最终改善临床结果。这两个UFCC方案建议通过经皮导管直接壁内植入，为冠心病患者开发左心功能不全/心力衰竭的细胞疗法。第一个主题是增强糖尿病患者的祖细胞功能。假说是，提高CD34细胞内NO的生物利用度将增强其改善心肌功能的固有能力。特异性靶点检测CD34细胞数量的增加；内源性NO对CD34细胞的作用；以及CD34细胞在低温保存和/或低氧条件下孵育是否改善了室壁运动或血流灌注异常。第二个方案中的假设是，等待心脏移植的患者提供了一个独特的机会来研究细胞治疗对功能的影响。特定的靶点测试骨骼肌母细胞(SKM)对心脏功能的影响是否依赖于细胞的存在，而不是对植入过程的反应。我们将确定在接受治疗和治疗3个月后的患者中是否有更多的存活细胞，并将使用SKM与方案1中优化的CD34细胞联合使用来衡量细胞治疗的效果。 由于这些研究将在等待移植的患者中进行，因此对移植的心脏和标记细胞的研究应该会产生关于细胞移植的命运和具体位置的新信息。这两个方案的新特点是，细胞将被非侵入性地标记和跟踪，并根据方案2中调查的移植心脏中的细胞类型进行组织学验证。UFCC的其他独特方面包括利用我们在相关领域的K30和T32计划提供的结构的培训核心，以及与波多黎各大学和工业界的合作。这项工作将提高我们对细胞疗法在冠心病和心力衰竭患者中的作用的理解。(摘要结束)

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)