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计划，特别是在干细胞和心力衰竭(HF)患者、左心室辅助装置(LVAD)和缺血性心肌病患者方面。来自心血管内科和胸科和心血管外科的高度凝聚力和合作的研究团队多年来在几个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，再加上数年来在细胞疗法方面开展的强大的临床前研究工作，为作为地区临床中心参与CCTRN提供了一个极好的平台。我们中心对干细胞进行L/11期研究的能力的例证是我们成功地在心力衰竭(Scipio)患者中进行了第一个c-kit+心脏干细胞的人体研究。使Scipio成为可能的相同的调查人员和基础设施将被用于CCTRN研究。在这里，我们建议Seneca(终末期心力衰竭的干细胞治疗)，在其中，我们将测试CD34+细胞或极小胚胎样细胞(VSEL)经冠状动脉内输送给终末期缺血性心肌病(ICM)患者的可行性和安全性(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，从而改善心功能、功能容量和整体生活质量，并使心肌功能恢复到可以考虑移植的程度。在目标3中，我们将确定患者的特征和干细胞功能的体外参数，这些参数与CD34+细胞和VSEL在改善体内左心功能方面的有效性(或缺乏)相关。Seneca将是第一个在人类身上进行VSEL的研究，也是第一个测试CD34+细胞在终末期缺血性心力衰竭中的作用的对照试验。因此，这一结果将是全新的，可能会为目前预后不佳的患者提供一个新的选择。因此，Seneca的潜在影响是相当大的。之前还没有关于LVADs和ICM患者的细胞治疗研究的报道，尽管这些患者正是最需要它的人。因此，Seneca将解决心脏病患者管理中的一个主要治疗缺口。这项试验有可能在治疗终末期缺血性心脏病方面提供一个新的临床突破。

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.