Cord Blood: Treatment for Acute Myocardial Infarction

脐带血：治疗急性心肌梗塞

• 批准号: 6789637
• 负责人: WILLIAM G MARSHALL
• 金额: $ 18.42万
• 依托单位: SANERON CCEL THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6789637
• 关键词: artificial immunosuppression; clinical research; cord blood; human tissue; myocardial infarction; nonhuman therapy evaluation; stem cell transplantation; swine; therapy design /development; transplantation immunology

DESCRIPTION (provided by applicant): Transplantation of human umbilical cord stem cells (hUCBC) has been shown to be effective in limiting infarct size and in the preservation of left ventricular function and anatomy in a rat model. These effects have been present in studies both utilizing and not utilizing immunosuppression. Whether immunosuppression will be required in a large animal model is unknown, as is the efficacy of transplantation of hUCBC in a large animal model. This data is critical in order to determine the risk:benefit ratio of this therapy, especially if immunosuppression is required; and in order to move this therapy into human clinical trials for the treatment of myocardial infarction and prevention of congestive heart failure which affects over 5 million patients in the U.S. This study is specifically designed to evaluate the effects of hUCBC transplantation following myocardial infarction on left ventricular function and anatomy and determine the necessity of immunosuppression in a porcine model. Forty-two animals will be studied; 6 animals will serve as controls (no myocardial infarction) and 36 animals will undergo myocardial infarction (MI). The MI group will consist of three (12 animals each) different treatment modalities (Group 1-no treatment, Group 2-treatment with Isolyte media injection into the infarct border zone, and Group 3-treatment with hUCBC injection into the infarct zone). Six animals in each treatment group will receive immunosuppression and six will receive no immunosuppression. Those animals that are designated for immunosuppression will receive cyclosporine 10 mg/kg twenty-four hours preoperatively and every day subsequently until sacrificed. The randomization will be blinded to pathologists, sonographers, and echocardiogram interpreters. LV function will be evaluated by echocardiography and invasive monitoring at 1, 2, and 4 wks and 2, 3, and 4 months. Animals will be sacrificed following evaluation and the heart tissue will be analyzed for infarct size, hUCBC engraftment, immunorejection, cardiac phenotype (using immunohistochemistry), and stem-cell derived endothelial cells. It is anticipated that the results from this study will assist in planning further studies for determination of the appropriate dosage, route, and timing of administration of hUCBC for the treatment of acute myocardial infraction to preserve left ventricular function and anatomy and prevent the development of congestive heart failure.

描述（由申请人提供）：在大鼠模型中，人脐带干细胞（hUCBC）移植已被证明在限制梗死面积和保存左心室功能和解剖结构方面有效。这些影响在使用和不使用免疫抑制的研究中都存在。在大型动物模型中是否需要免疫抑制尚不清楚，在大型动物模型中移植hUCBC的效果也不清楚。这些数据对于确定该疗法的风险：收益比至关重要，特别是在需要免疫抑制的情况下；为了将这种治疗方法用于治疗心肌梗死和预防充血性心力衰竭的人体临床试验，美国有500多万患者受到心肌梗死的影响。本研究专门设计用于评估心肌梗死后hUCBC移植对左心室功能和解剖结构的影响，并确定猪模型中免疫抑制的必要性。42只动物将被研究；6只动物作为对照（无心肌梗死），36只动物作为心肌梗死（MI）。心肌梗死组将由三个不同的治疗方式组成（每个组12只动物）（第1组-不治疗，第2组-在梗死区边界注射异溶质培养基，第3组-在梗死区注射hUCBC）。每组6只进行免疫抑制，6只不进行免疫抑制。指定免疫抑制动物术前24小时给予环孢素10 mg/kg，此后每天给予，直至牺牲。随机分组将不包括病理学家、超声医师和超声心动图翻译。在1、2、4周和2、3、4个月时通过超声心动图和有创监测评估左室功能。评估后，动物将被处死，心脏组织将被分析梗死面积、hUCBC植入、免疫排斥、心脏表型（使用免疫组织化学）和干细胞来源的内皮细胞。预计本研究的结果将有助于制定进一步的研究计划，以确定适当的剂量、途径和给药时间，以保护左心室功能和解剖结构，防止充血性心力衰竭的发展。