Cardiopoietic Stem Cell Therapy in Heart Failure
Cardiopoietic Stem Cell Therapy in Heart Failure
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DOI：
10.1016/j.jacc.2013.02.071
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发表时间：
2013-06-11
影响因子：
24
通讯作者：
Terzic, Andre
中科院分区：
文献类型：
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作者：
Bartunek, Jozef;Behfar, Atta;Terzic, Andre
目的评价自体骨髓间充质干细胞治疗慢性心力衰竭的可行性和安全性，探讨其治疗慢性心力衰竭的有效指标。背景：在临床前心力衰竭模型中，心源性干细胞治疗可改善左心功能，钝化病理重建。方法C-CURE(心衰心脏干细胞治疗)试验是一项前瞻性、多中心、随机试验，用于接受标准护理或标准护理+谱系特异性干细胞治疗的缺血性心力衰竭患者。在细胞治疗组中，采集骨髓，并将分离的间充质干细胞暴露在心源性鸡尾酒中。在良好的制造规范下，符合释放标准的来源的心脏干细胞通过在左心室机电标测指导下的心内膜心肌注射被输送。数据采集和分析采用盲法进行。主要终点是2年随访的可行性/安全性。次要终点包括心脏结构/功能和治疗后6个月的整体临床表现。结果每例患者均实现了以间充质干细胞鸡尾酒为基础的预充，达到75%的剂量，100%的病例无并发症。没有证据表明，心脏或全身毒性增加的心脏造血细胞治疗。与单纯护理标准(从27.8+/-2.0%到28.0+/-1.8%，p<；0.0001)相比，细胞疗法使左心室射血分数(从27.5+/-1.0%提高到34.5+/-1.1%)，并且与左心室收缩末期容量(-24.8+/-3.0ml比-8.8+/-3.9ml，p<；0.001)的减少有关。细胞疗法还改善了6分钟步行距离(+62+/-18m比-15+/-20m，p<；0.01)，并提供了包括心脏参数、纽约心脏协会功能分级、生活质量、体能、住院和无事件生存的优越综合临床评分。结论C-CURE试验在细胞治疗中实施了谱系指导的范式。心脏干细胞疗法被发现是可行和安全的，有迹象表明对慢性心力衰竭有益，值得进行明确的临床评估。(C-Cure临床试验；NCT00810238)(C)2013年，美国心脏病学会基金会
Objectives This study sought to evaluate the feasibility and safety of autologous bone marrow-derived and cardiogenically oriented mesenchymal stem cell therapy and to probe for signs of efficacy in patients with chronic heart failure.Background In pre-clinical heart failure models, cardiopoietic stem cell therapy improves left ventricular function and blunts pathological remodeling.Methods The C-CURE (Cardiopoietic stem Cell therapy in heart failURE) trial, a prospective, multicenter, randomized trial, was conducted in patients with heart failure of ischemic origin who received standard of care or standard of care plus lineage-specified stem cells. In the cell therapy arm, bone marrow was harvested and isolated mesenchymal stem cells were exposed to a cardiogenic cocktail. Derived cardiopoietic stem cells, meeting release criteria under Good Manufacturing Practice, were delivered by endomyocardial injections guided by left ventricular electromechanical mapping. Data acquisition and analysis were performed in blinded fashion. The primary endpoint was feasibility/safety at 2-year follow-up. Secondary endpoints included cardiac structure/function and measures of global clinical performance 6 months post-therapy.Results Mesenchymal stem cell cocktail-based priming was achieved for each patient with the dose attained in 75% and delivery without complications in 100% of cases. There was no evidence of increased cardiac or systemic toxicity induced by cardiopoietic cell therapy. Left ventricular ejection fraction was improved by cell therapy (from 27.5 +/- 1.0% to 34.5 +/- 1.1%) versus standard of care alone (from 27.8 +/- 2.0% to 28.0 +/- 1.8%, p < 0.0001) and was associated with a reduction in left ventricular end-systolic volume (-24.8 +/- 3.0 ml vs. -8.8 +/- 3.9 ml, p < 0.001). Cell therapy also improved the 6-min walk distance (+62 +/- 18 m vs. -15 +/- 20 m, p < 0.01) and provided a superior composite clinical score encompassing cardiac parameters in tandem with New York Heart Association functional class, quality of life, physical performance, hospitalization, and event-free survival.Conclusions The C-CURE trial implements the paradigm of lineage guidance in cell therapy. Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in chronic heart failure, meriting definitive clinical evaluation. (C-Cure Clinical Trial; NCT00810238) (C) 2013 by the American College of Cardiology Foundation