STEM CELL MEDIATED ANGIOGENESIS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。目前，临床上还没有有效的方法来增强严重周围血管疾病(PVD)患者的动脉血流灌注。最近在骨髓和外周血的单个核细胞中发现了表达CD34、CD133和VEGFR-2表面抗原的内皮祖细胞。在日本的临床前研究和临床试验中，内皮祖细胞已被证明参与血管生成和血管重塑。这项研究是FDA和IRB批准的I期临床试验，目的是确定肌肉注射含有祖细胞群的自体骨髓单个核细胞(MNC)是否在肢体威胁缺血的患者中诱导血管生成反应，而没有任何明显的不良事件。最初，将招募10名患者来确定安全性。治疗的安全性将由数据安全监测委员会监测，并通过风险-效益分析确定。如果确定手术是安全的，将再招募10名患者，以确定治疗效果，使用客观的措施，动脉灌注的治疗小腿。血流灌注的主要测量将是动脉造影术和踝臂压力记录。二次血流灌注测量将包括核磁共振、静息疼痛评估、经皮血氧饱和度测量和伤口愈合。这项建议的目的是确定干细胞介导的血管生成是否是增加血管疾病患者腿部血流量的安全有效的手段。此外，从这项研究中获得的信息将对未来基于细胞的心血管疾病疗法的设计至关重要。

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.