Cord Blood: Treatment for Acute Myocardial Infarction

描述（由申请人提供）：在大鼠模型中，人脐带干细胞（hUCBC）的移植已被证明在限制梗死面积和保护左心室功能和解剖结构方面有效。这些效应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是未知的，在大型动物模型中移植hUCBC的功效也是未知的。这些数据对于确定该疗法的风险：获益比至关重要，尤其是在需要免疫抑制的情况下;并且为了将这种疗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，在美国，充血性心力衰竭影响超过500万患者。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在猪模型中确定免疫抑制的必要性。将对42只动物进行研究; 6只动物将作为对照（无心肌梗死），36只动物将发生心肌梗死（MI）。MI组将由三种（每种12只动物）不同的治疗方式组成（第1组-无治疗，第2组-用Isolyte培养基注射到梗塞边缘区中治疗，和第3组-用hUCBC注射到梗塞区中治疗）。每个处理组中的6只动物将接受免疫抑制，6只将不接受免疫抑制。指定进行免疫抑制的动物将在术前24小时和随后每天接受10 mg/kg环孢素，直至处死。随机化将对病理学家、超声检查员和超声心动图判读员设盲。将在第1、2和4周以及第2、3和4个月通过超声心动图和有创监测评价LV功能。评价后处死动物，分析心脏组织的梗死面积、hUCBC植入、免疫排斥、心脏表型（使用免疫组织化学）和干细胞衍生的内皮细胞。预计本研究的结果将有助于计划进一步的研究，以确定hUCBC治疗急性心肌梗死的适当剂量、途径和给药时间，以保护左心室功能和解剖结构并预防充血性心力衰竭的发展。

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.