UFCC for Cardiovascular Cell Therapy Research Network

描述（由申请人提供）： 本申请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）细胞治疗是一个令人兴奋的概念，用于替代非收缩性心肌及其血管。但是，尽管进行了大量的临床前和可行性临床研究，但将这些发现转化为改善患者预后的能力仍然落后。为了满足这一需求，UFCC利用在干细胞生物学，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临床试验计划建立UF程序。我们在多中心NHLBI和其他试验中成功合作，以测试改善心脏灌注或功能并评估临床结局的策略，这是一个长期且有据可查的记录。 我们中心提出，增强祖细胞功能将改善CAD心力衰竭患者的心功能，并最终改善临床结局。这两个UFCC方案建议通过经皮导管直接壁内植入，为患有左心室功能不全/心力衰竭的CAD患者开发细胞治疗。其中第一个解决了增强糖尿病患者的祖细胞功能。该假说是，改善CD 34+细胞内的NO生物利用度将增强其改善心肌功能的固有能力。具体目的是测试增加CD 34+细胞数量;向CD 34+细胞施用内源性NO;以及在低温和/或缺氧条件下孵育CD 34+细胞是否改善了室壁运动或灌注异常。第二个方案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。具体目的是测试骨骼肌成肌细胞（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个月时接受治疗和重新给药的患者中是否有更多数量的存活细胞，并将测量使用方案1中优化的SkM与CD 34+细胞联合给药的细胞疗法的效果。 由于这些研究将在等待移植的患者中进行，因此对移植心脏和标记细胞的研究应该会产生关于细胞植入物的命运和具体位置的新信息。这两种方案的新特征是，将对细胞进行标记和非侵入性跟踪，并在方案2中研究的心脏移植中根据细胞类型进行组织学验证。UFCC的其他独特方面包括培训核心，利用我们在相关领域的K30和T32计划以及与波多黎各大学和行业的合作提供的结构。这项工作将提高我们对细胞治疗在CAD和心力衰竭患者中的作用的理解。 (End摘要）

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)