心肌梗死后冠状动脉内的心细胞：CADUCEUS 试验（CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction）最终 1 年结果中治疗再生的证据。
Intracoronary cardiosphere-derived cells after myocardial infarction: evidence of therapeutic regeneration in the final 1-year results of the CADUCEUS trial (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction).
机构信息
Cedars-Sinai Heart Institute, Los Angeles, California.
Division of Cardiology, Department of Medicine, Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, Illinois.
出版信息
J Am Coll Cardiol. 2014 Jan 21;63(2):110-22. doi: 10.1016/j.jacc.2013.08.724. Epub 2013 Sep 11.
OBJECTIVES
This study sought to report full 1-year results, detailed magnetic resonance imaging analysis, and determinants of efficacy in the prospective, randomized, controlled CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial.
BACKGROUND
Cardiosphere-derived cells (CDCs) exerted regenerative effects at 6 months in the CADUCEUS trial. Complete results at the final 1-year endpoint are unknown.
METHODS
Autologous CDCs (12.5 to 25 × 10(6)) grown from endomyocardial biopsy specimens were infused via the intracoronary route in 17 patients with left ventricular dysfunction 1.5 to 3 months after myocardial infarction (MI) (plus 1 infused off-protocol 14 months post-MI). Eight patients were followed as routine-care control patients.
RESULTS
In 13.4 months of follow-up, safety endpoints were equivalent between groups. At 1 year, magnetic resonance imaging revealed that CDC-treated patients had smaller scar size compared with control patients. Scar mass decreased and viable mass increased in CDC-treated patients but not in control patients. The single patient infused 14 months post-MI responded similarly. CDC therapy led to improved regional function of infarcted segments compared with control patients. Scar shrinkage correlated with an increase in viability and with improvement in regional function. Scar reduction correlated with baseline scar size but not with a history of temporally remote MI or time from MI to infusion. The changes in left ventricular ejection fraction in CDC-treated subjects were consistent with the natural relationship between scar size and ejection fraction post-MI.
CONCLUSIONS
Intracoronary administration of autologous CDCs did not raise significant safety concerns. Preliminary indications of bioactivity include decreased scar size, increased viable myocardium, and improved regional function of infarcted myocardium at 1 year post-treatment. These results, which are consistent with therapeutic regeneration, merit further investigation in future trials. (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction [CADUCEUS]; NCT00893360).
目的
本研究旨在报告前瞻性、随机、对照 CADUCEUS（心脏球源性自体干细胞逆转心室功能障碍）试验的完整 1 年结果、详细的磁共振成像分析结果和疗效决定因素。
背景
CADUCEUS 试验中，心脏球源性细胞（CDCs）在 6 个月时产生了再生作用。最终 1 年终点的完整结果尚不清楚。
方法
从心肌梗死（MI）后 1.5 至 3 个月的患者的心肌活检标本中培养的自体 CDCs（12.5 至 25×10(6)）经冠状动脉途径输注，17 例左心室功能障碍患者接受了治疗（另有 1 例患者在 MI 后 14 个月时不符合方案规定接受了输注）。8 例患者作为常规治疗对照组。
结果
在 13.4 个月的随访中，两组的安全性终点无差异。在 1 年时，磁共振成像显示，与对照组相比，CDC 治疗组的疤痕大小较小。在 CDC 治疗组中，疤痕质量减少，存活质量增加，但在对照组中没有。14 个月后 MI 时输注的单个患者也有类似反应。与对照组相比，CDC 治疗导致梗死节段的局部功能改善。疤痕收缩与存活质量的增加和局部功能的改善相关。疤痕减少与基线疤痕大小相关，但与时间上相隔较远的 MI 史或从 MI 到输注的时间无关。CDC 治疗组左心室射血分数的变化与 MI 后疤痕大小与射血分数之间的自然关系一致。
结论
冠状动脉内给予自体 CDCs 没有引起明显的安全性问题。初步的生物活性迹象包括治疗后 1 年时疤痕大小减小、存活心肌增加和梗死心肌的局部功能改善。这些结果与治疗性再生一致，值得在未来的试验中进一步研究。（心脏球源性自体干细胞逆转心室功能障碍 [CADUCEUS]；NCT00893360）。
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