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).
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).
复制标题
DOI：
10.1016/j.jacc.2013.08.724
复制
发表时间：
2014-01-21
影响因子：
24
通讯作者：
Marban, Eduardo
中科院分区：
文献类型：
--
作者：
Malliaras, Konstantinos;Makkar, Raj R.;Smith, Rachel R.;Cheng, Ke;Wu, Edwin;Bonow, Robert O.;Marban, Linda;Mendizabal, Adam;Cingolani, Eugenio;Johnston, Peter V.;Gerstenblith, Gary;Schuleri, Karl H.;Lardo, Albert C.;Marban, Eduardo
本研究旨在报告前瞻性、随机、对照的CADUCEUS（心肌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以及疗效的决定因素。
在CADUCEUS试验中，心肌球源性细胞（CDCs）在6个月时发挥了再生作用。最终1年终点的完整结果尚不清楚。
从心内膜心肌活检标本中培养的自体CDCs（1250万 - 2500万）在心肌梗死（MI）后1.5 - 3个月通过冠状动脉内途径注入17名左心室功能障碍患者体内（另有1名在MI后14个月违反方案进行了注入）。8名患者作为常规护理对照患者进行随访。
在13.4个月的随访中，两组之间的安全性终点相当。1年时，磁共振成像显示，与对照患者相比，CDC治疗的患者疤痕更小。CDC治疗的患者疤痕质量下降，存活心肌质量增加，但对照患者没有这些变化。MI后14个月注入的那1名患者也有类似反应。与对照患者相比，CDC治疗使梗死节段的局部功能得到改善。疤痕缩小与存活心肌增加以及局部功能改善相关。疤痕减少与基线疤痕大小相关，但与既往远期MI病史或从MI到注入的时间无关。CDC治疗患者的左心室射血分数变化与MI后疤痕大小和射血分数之间的自然关系相符。
冠状动脉内注射自体CDCs没有引起重大的安全问题。生物活性的初步迹象包括治疗后1年疤痕大小减小、存活心肌增加以及梗死心肌的局部功能改善。这些与治疗性再生相符的结果值得在未来的试验中进一步研究。
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. Cardiosphere-derived cells (CDCs) exerted regenerative effects at 6 months in the CADUCEUS trial. Complete results at the final 1-year endpoint are unknown. Autologous CDCs (12.5 to 25 × 106) 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. 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. 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.
登录
查看更多内容
影响因子：
168.9
作者：
Makkar, Raj R.;Smith, Rachel R.;Cheng, Ke;Malliaras, Konstantinos;Thomson, Louise E. J.;Berman, Daniel;Czer, Lawrence S. C.;Marban, Linda;Mendizabal, Adam;Johnston, Peter V.;Russell, Stuart D.;Schuleri, Karl H.;Lardo, Albert C.;Gerstenblith, Gary;Marban, Eduardo
通讯作者：
Marban, Eduardo
影响因子：
24
作者：
Hare, Joshua M.;Traverse, Jay H.;Henry, Timothy D.;Dib, Nabil;Strumpf, Robert K.;Schulman, Steven P.;Gerstenblith, Gary;DeMaria, Anthony N.;Denktas, Ali E.;Gammon, Roger S.;Hermiller, James B., Jr.;Reisman, Mark A.;Schaer, Gary L.;Sherman, Warren
通讯作者：
Sherman, Warren
影响因子：
24
作者：
Amado, LC;Gerber, BL;Lima, JAC
通讯作者：
Lima, JAC
影响因子：
24
作者：
Greupner, Johannes;Zimmermann, Elke;Dewey, Marc
通讯作者：
Dewey, Marc
影响因子：
168.9
作者：
Janssens, S;Dubois, C;Van de Werf, F
通讯作者：
Van de Werf, F