Utility of Autologous and Allogeneic Cell Therapy for Peripheral Arterial Disease

自体和同种异体细胞疗法在外周动脉疾病中的应用

• 批准号: 8622215
• 负责人: KEITH LEONARD MARCH
• 金额: $ 53.11万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-15 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8622215
• 关键词: Addendum; Address; Adipocytes; Adipose tissue; Adverse event; Age; Allogenic; Amputation; Area; Autologous; Blinded; Blood Circulation; Blood Vessels; Blood flow; Bone Marrow; Cardiovascular system; Categories; Cell Separation; Cell Therapy; Cell Transplants; Cell physiology; Cells; Cessation of life; Characteristics; Clinical; Clinical Trials; Clinics and Hospitals; Complement; Data; Devices; Dimensions; Disease; Double-Blind Method; Effectiveness; Event; Health; Heart; Heart Diseases; Hospitals; Immunocompetent; Indiana; Injection of therapeutic agent; Ischemia; Leg; Life; Limb Salvage; Limb structure; Lower Extremity; Measures; Medical center; Mononuclear; Muscle; Myocardial; Pain; Patients; Performance; Perfusion; Peripheral arterial disease; Pharmaceutical Preparations; Phase; Phase III Clinical Trials; Placebos; Population; Protocols documentation; Randomized; Rest; Risk; Safety; Source; Staging; Stem cells; Stromal Cells; Syndrome; System; Testing; Therapeutic Studies; Time; Tissues; Training; Ulcer; Umbilical Cord Blood; Universities; Veterans; Work; base; comparative efficacy; cost; cytokine; design; disability; experience; high risk; improved; indexing; novel; pre-clinical; programs; randomized placebo controlled trial; regenerative

DESCRIPTION (provided by applicant): The Indiana Regional Cardiovascular Cell Therapy Center (IRCCTC) will extend the work of the Cardiovascular Cell Therapy Research Network, particularly in the area of peripheral arterial disease (PAD). Critical limb ischemia (CLI) results in at least 50,000 amputations annually, with a cost estimated at $4.3 billion/year. In a recent Phase l/ll trial we have demonstrated safety and feasibility of intra-muscular injection of autologous bone marrow mononuclear cells (ABMNC) in patients with CLI, and provided initial evidence that this treatment improves amputation-free survival at one year. Although these results are promising, there is an opportunity to improve the effectiveness of cell therapy for CLI by identifying more potent sources of progenitor cells and by evaluating functional characteristics of transplanted cells. While many cardiovascular cell-based trials have focused on ABMNC, adipose stromal cells (ASCs) have demonstrated qualities particularly suitable for promoting limb salvage in CLI. In addition, cord blood mononuclear cells (CBMNC) have been shown to include vasculogenic endothelial progenitor cells, to augment perfusion in ischemic limbs, and to be tolerated by an immunocompetent host. CLI presents an excellent opportunity to examine these two readily accessible cell populations with regard to suitability for cardiovascular cell therapy, in that there exist no other options fo salvage of the index limb, potential adverse events are not immediately life-threatening, and tissue can be obtained for analysis in the event of amputation. Also, mechanisms promoting limb salvage in CLI have relevance to myocardial ischemic syndromes. In this application for a new Regional Center, we propose two protocols, respectively evaluating allogeneic cord blood mononuclear cells and adipose stromal cells as potential therapies for CLI. Aim 1 will evaluate whether CBMNC are superior to placebo in promoting amputation-free survival at 1 year in subjects with critical limb ischemia of Rutherford Category 4, and no /high-risk options for standard revascularization. Aim 2 will test the hypothesis that adipose stromal cells (ASCs) are safe and may increase time to amputation in subjects with critical limb ischemia and ulcers / tissue loss (Rutherford Category 5-6).

描述（由申请人提供）： 印第安纳州区域心血管细胞疗法中心（IRCCTC）将扩大心血管细胞治疗研究网络的工作，特别是在周围动脉疾病（PAD）领域。关键的肢体缺血（CLI）每年至少会导致50,000个截肢，估计成本为43亿美元/年。在最近的L/LL试验中，我们证明了安全性和 自体骨髓单核细胞（ABMNC）在CLI患者中的可行性，并提供了初始证据，表明该治疗可改善一年的无截肢生存率。尽管这些结果是有希望的，但有机会通过鉴定更有效的祖细胞来源并评估移植细胞的功能特征来提高CLI的有效性。尽管许多基于心血管细胞的试验都集中在ABMNC上，但脂肪基质细胞（ASC）表现出特别适合在CLI中促进肢体抢救的品质。此外，脐带血单核细胞（CBMNC）已显示包括血管生成内皮祖细胞，增强缺血性肢体灌注，并由免疫能力的宿主耐受。 CLI提供了一个很好的机会，可以检查这两个容易获得的细胞种群，以适合心血管细胞疗法，因为该指数肢体没有其他选择。在截肢时获得分析。同样，促进CLI中肢体救助的机制与心肌缺血综合征相关。在新的区域中心的应用中，我们提出了两种方案，分别评估了同种异体脐带血单核细胞和脂肪基质细胞作为CLI的潜在疗法。 AIM 1将评估CBMNC在卢瑟福4类关键的肢体缺血的受试者中促进1年的无截肢生存方面是否优于安慰剂，并且没有标准血运重建的高风险选择。 AIM 2将检验以下假设：脂肪基质细胞（ASC）是安全的，并且可能会增加临界肢体缺血和溃疡 /组织损失受试者的截肢时间（Rutherford类别5-6）。