PDF(Pubmed)
Abstract：
UNASSIGNED: With the expected increase in patients with heart failure and ischemic 15 cardiomyopathy, the development of myocardial regenerative medicine using cell transplantation as a novel treatment method is progressing. This first-in-human clinical trial aimed to confirm the safety of cardiomyocyte patch transplantation derived from allogeneic induced pluripotent stem (iPS) cells based on the results of several preclinical studies.
UNASSIGNED: The inclusion criteria were left ventricular ejection fraction of 35% or less; heart failure symptoms of New York Heart Association class III or higher despite existing therapies such as revascularization; and a 1-year observation period that included a 3-month immunosuppressive drug administration period after transplantation of iPS cell-derived cardiomyocyte patches to evaluate adverse events, cardiac function, myocardial blood flow, heart failure symptoms, and immune response.
UNASSIGNED: In the first three cases of this trial, no transplanted cell-related adverse events were observed during the 1-year observation period, and improvement in heart failure symptoms was observed. In addition, improvements in left ventricular contractility and myocardial blood flow were observed in two of the three patients. Regarding immune response, an increase in transplant cell-specific antibody titer was observed in all three patients after immunosuppressive drug administration. In one patient with poor improvement in cardiac function and myocardial blood flow, an increase in antibody titer against HLA-DQ was observed even before cell transplantation.
UNASSIGNED: Our case findings demonstrate that the transplantation of iPS cell-derived cardiomyocyte patches for ischemic cardiomyopathy can be safely performed; however, further investigation of the therapeutic effect and its relationship with an immune response is needed by accumulating the number of patients through continued clinical trials.
UNASSIGNED: The inclusion criteria were left ventricular ejection fraction of 35% or less; heart failure symptoms of New York Heart Association class III or higher despite existing therapies such as revascularization; and a 1-year observation period that included a 3-month immunosuppressive drug administration period after transplantation of iPS cell-derived cardiomyocyte patches to evaluate adverse events, cardiac function, myocardial blood flow, heart failure symptoms, and immune response.
UNASSIGNED: In the first three cases of this trial, no transplanted cell-related adverse events were observed during the 1-year observation period, and improvement in heart failure symptoms was observed. In addition, improvements in left ventricular contractility and myocardial blood flow were observed in two of the three patients. Regarding immune response, an increase in transplant cell-specific antibody titer was observed in all three patients after immunosuppressive drug administration. In one patient with poor improvement in cardiac function and myocardial blood flow, an increase in antibody titer against HLA-DQ was observed even before cell transplantation.
UNASSIGNED: Our case findings demonstrate that the transplantation of iPS cell-derived cardiomyocyte patches for ischemic cardiomyopathy can be safely performed; however, further investigation of the therapeutic effect and its relationship with an immune response is needed by accumulating the number of patients through continued clinical trials.
摘要：
■随着心力衰竭和缺血性心肌病患者的预期增加，使用细胞移植作为一种新的治疗方法的心肌再生医学的发展正在取得进展。这项首次人体临床试验旨在根据几项临床前研究的结果确认源自同种异体诱导多能干细胞（iPS）的心肌细胞贴片移植的安全性。
■纳入标准为左心室射血分数为35%或更低；尽管现有的治疗方法如血运重建，但纽约心脏协会的心力衰竭症状为III级或更高；以及1年的观察期，包括在移植iPS细胞源性心肌细胞贴片后3个月的免疫抑制药物给药期，以评估不良事件，心功能,心肌血流量,心力衰竭症状,和免疫反应。
■在该审判的前三起案件中，在1年的观察期内，没有观察到移植细胞相关的不良事件，并观察到心力衰竭症状的改善。此外,3例患者中有2例观察到左心室收缩力和心肌血流量改善.关于免疫反应，在给予免疫抑制药物后,3例患者均观察到移植细胞特异性抗体滴度升高.在一名心功能和心肌血流量改善不佳的患者中，甚至在细胞移植之前观察到针对HLA-DQ的抗体滴度增加.
■我们的病例研究结果表明，iPS细胞源性心肌细胞补片移植治疗缺血性心肌病是安全的；然而，需要通过持续的临床试验积累患者数量来进一步研究治疗效果及其与免疫反应的关系.
■纳入标准为左心室射血分数为35%或更低；尽管现有的治疗方法如血运重建，但纽约心脏协会的心力衰竭症状为III级或更高；以及1年的观察期，包括在移植iPS细胞源性心肌细胞贴片后3个月的免疫抑制药物给药期，以评估不良事件，心功能,心肌血流量,心力衰竭症状,和免疫反应。
■在该审判的前三起案件中，在1年的观察期内，没有观察到移植细胞相关的不良事件，并观察到心力衰竭症状的改善。此外,3例患者中有2例观察到左心室收缩力和心肌血流量改善.关于免疫反应，在给予免疫抑制药物后,3例患者均观察到移植细胞特异性抗体滴度升高.在一名心功能和心肌血流量改善不佳的患者中，甚至在细胞移植之前观察到针对HLA-DQ的抗体滴度增加.
■我们的病例研究结果表明，iPS细胞源性心肌细胞补片移植治疗缺血性心肌病是安全的；然而，需要通过持续的临床试验积累患者数量来进一步研究治疗效果及其与免疫反应的关系.
