University of Louisville Regional Clinical Center for the CCTRN

描述（由申请人提供）： 路易斯维尔大学/犹太医院在心血管医学方面拥有非常活跃的基础和临床研究项目，特别是在干细胞和心力衰竭（HF）患者，左心室辅助装置（LVAD）和缺血性心肌病领域。来自心血管内科和胸心血管外科的一支高度凝聚力和学院式的研究团队多年来在多项多中心试验中卓有成效地工作，表现出色。现有的临床基础设施，加上多年来对细胞疗法进行的强大的临床前研究工作，为参与CCTRN作为区域临床中心提供了一个极好的平台。我们中心进行干细胞I/II期研究的能力通过我们在HF患者中进行c-kit+心脏干细胞的首次人体研究（SCIPIO）的成功来例证。使SCIPIO成为可能的相同研究者和基础设施将用于CCTRN研究。在这里，我们提出了SENECA（StEm细胞治疗终末期心脏衰竭），其中我们将测试在植入LVAD后向终末期缺血性心肌病（ICM）患者冠状动脉内递送CD 34+细胞或极小胚胎样细胞（VSEL）的可行性和安全性（目标1）和有效性（目标2）。我们的假设是，细胞治疗将促进受损心肌的修复和再生，从而改善心脏功能、功能能力和整体生活质量，并使心肌功能恢复到允许考虑LVAD重建的程度。在目的3中，我们将鉴定与CD 34+细胞和VSEL在体内改善LV功能的有效性（或缺乏有效性）相关的患者特征和干细胞功能的体外参数。SENECA将是第一个在人类中进行的VSEL研究，也是第一个测试CD 34+细胞在终末期缺血性HF中作用的对照试验。因此，这些结果将是全新的，并可能为目前预后不良的患者提供新的选择。因此，SENECA的潜在影响是相当大的。之前没有关于LVAD和ICM患者的细胞治疗研究报道，尽管这些患者最需要它。因此，SENECA将解决心脏病患者管理中的主要治疗差距。这项试验有可能为终末期缺血性心脏病的治疗提供一种新的临床突破。

DESCRIPTION (provided by applicant): The University of Louisville/Jewish Hospital has a remarkably vibrant basic and clinical research program in cardiovascular medicine, particularly in the area of stem cells and patients with heart failure (HF), left ventricular assist devices (LVADs), and ischemic cardiomyopathy. A highly cohesive and collegial team of investigators from the Divisions of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery has worked productively for many years in several multicenter trials, with outstanding performance. This existing clinical infrastructure, coupled with the strong preclinical research work conducted on cell-based therapies for several years, provides a superb platform for participation in the CCTRN as a Regional Clinical Center. The ability of our Center to carry out Phase l/ll studies of stem cells is exemplified by our success i performing the first in-human study of c-kit+ cardiac stem cells in patients with HF (SCIPIO). The same investigators and the infrastructure that made SCIPIO possible will be leveraged for the CCTRN studies. Here we propose SENECA (StEm cell treatmeNt for End stage CArdiac failure), in which we will test the feasibility and safety (Aim 1) and efficacy (Aim 2) of intracoronary delivery of CD34+ cells or very small embryonic-like cells (VSELs) to patients with end-stage ischemic cardiomyopathy (ICM) following implantation of an LVAD. Our hypothesis is that cell therapy will promote repair and regeneration of the injured myocardium, resulting in improved cardiac function, functional capacity, and overall quality of life, and recovery of myocardial function to a degree that permits consideration of LVAD explantation. In Aim 3, we will identify patient characteristics and in vitro parameters of stem cell function that are associated with effectiveness (or lack thereof) of CD34+ cells and VSELs in improving LV function in vivo. SENECA will be the first study of VSELs in humans and the first controlled trial to test the effects of CD34+ cells in end-stage ischemic HF. Therefore, the results will be entirely novel and may provide a new option for patients who currently have a dismal prognosis. Thus, the potential impact of SENECA is considerable. No cell therapy study has ever been reported before in patients with LVADs and ICM, although these are the very patients who need it the most. Therefore, SENECA will address a major therapeutic gap in the management of cardiac patients. This trial has the potential to provide a novel clinical breakthrough in the treatment of end-stage ischemic heart disease.