STEM CELL MEDIATED ANGIOGENESIS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。目前，对于严重周围血管疾病（PVD）患者，尚无临床有效的动脉灌注增强方法。内皮祖细胞（Endothelial progenitor cells, EPCs）表达表面抗原CD34、CD133和VEGFR-2，最近在骨髓和外周血的单核细胞部分被发现。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。本研究是一项I期临床试验，经FDA和irb批准，目的是确定肌肉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-收益分析确定。如果确定手术是安全的，将再招募10名患者，使用治疗腿动脉灌注的客观测量来确定治疗效果。血流灌注的主要措施是动脉造影和踝肱压记录。二次灌注测量包括MRI、静息疼痛评估、经皮氧测量和伤口愈合。这项提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.