STEM CELL MEDIATED ANGIOGENESIS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目前，没有临床上有效的方法来增强严重外周血管疾病（PVD）患者的动脉灌注。最近在骨髓和外周血的单个核细胞部分中发现了表达表面抗原CD 34、CD 133和VEGFR-2的内皮祖细胞（EPCs）。在日本的临床前研究和临床试验中，EPCs已被证明参与血管生成和血管重塑。本研究是一项I期、FDA和IRB批准的临床试验，目的是确定肌内注射含有祖细胞群的自体骨髓单核细胞（MNC）是否能诱导肢体威胁性缺血患者的血管生成反应，而无任何显著不良事件。最初，将招募10名患者以确定安全性。治疗的安全性将由数据安全监测委员会监测，并通过风险-受益分析确定。如果确定手术是安全的，则将招募另外10名患者，以使用经治疗腿部的动脉灌注的客观测量来确定治疗的有效性。灌注的主要测量将是动脉造影和踝臂压力记录。灌注的次要测量将包括MRI、静息痛评估、经皮氧测量和伤口愈合。这项建议的目的是确定干细胞介导的血管生成是否是一种安全有效的增加血管疾病患者腿部血流量的方法。此外，从这项研究中获得的信息将在未来基于细胞的心血管疾病疗法的设计中发挥关键作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Presently, there are no clinically effective methods to enhance arterial perfusion for patients with severe peripheral vascular disease (PVD). Endothelial progenitor cells (EPCs) expressing the surface antigens CD34, CD133 and VEGFR-2 have recently been discovered in the mononuclear cell fraction of bone marrow and peripheral blood. EPCs have been shown to participate in angiogenesis and vascular remodeling in preclinical studies and in a clinical trial in Japan. The purpose of this study, a phase I, FDA- and IRB-approved clinical trial, is to determine if intramuscular injection of autologous bone marrow mononuclear cells (MNCs) containing progenitor cell populations induces an angiogenic response in patients with limb threatening ischemia without any significant adverse events. Initially, ten patients will be recruited to determine safety. Safety of the therapy will be monitored by a Data Safety Monitoring Board and determined by a risk-benefit analysis. If the procedure is determined to be safe, ten additional patients will be recruited to determine efficacy of treatment using objective measures of arterial perfusion of the treated leg. Primary measures of perfusion will be arteriography and ankle- brachial pressure recording. Secondary measures of perfusion will include MRI, assessment of rest pain, transcutaneous oxygen measurements and wound healing. The purpose of this proposal is to determine if stem cell mediated angiogenesis is a safe and effective means of increasing blood flow in the legs of patients with vascular disease. Furthermore, the information gained from this study will be critical in the design of future cell-based therapies for cardiovascular disease.