A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction.
A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction.
复制标题
DOI：
10.1016/j.jacc.2009.06.055
复制
发表时间：
2009-12-08
影响因子：
24
通讯作者：
Sherman, Warren
中科院分区：
文献类型：
--
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
我们的目的是探讨静脉注射同种异体人骨髓间充质干细胞（hMSCs）在心肌梗死（MI）患者中的安全性和有效性。骨髓来源的hMSCs可以改善MI的后果，并且具有制备容易、由于免疫豁免而异基因使用、归巢至损伤组织的能力以及广泛的临床前支持的优点。我们进行了静脉内同种异体hMSC的双盲、安慰剂对照、剂量范围（0.5、1.6和5百万个细胞/kg）安全性试验（Prochymal，Osiris Therapeutics，Inc.，巴尔的摩，马里兰州）再灌注MI患者（n = 53）。主要终点是6个月内治疗后出现的不良事件的发生率。通过超声心动图和磁共振成像确定的射血分数和左心室容积是探索性疗效终点。hMSC治疗组（每例患者5.3例）和安慰剂治疗组（每例患者7.0例）的不良事件发生率相似，肾脏、肝脏和血液学实验室指标无差异。动态心电图监测显示hMSC治疗患者的室性心动过速发作减少（p = 0.025），肺功能测试显示1秒用力呼气量改善（p = 0.003）。所有患者的总体症状评分（p = 0.027）和前壁心肌梗死患者重要亚组的射血分数在hMSCs组均显著优于安慰剂组。在心脏磁共振成像子研究中，hMSC治疗，而不是安慰剂，增加左心室射血分数，并导致逆转重构。静脉注射同种异体hMSCs在急性心肌梗死患者中是安全的。本试验提供了同种异体骨髓源性干细胞在梗死后患者中的关键安全性和临时疗效数据。（成人间充质干细胞[MSC]治疗急性心肌梗死的安全性研究; NCT 00114452）
Our aim was to investigate the safety and efficacy of intravenous allogeneic human mesenchymal stem cells (hMSCs) in patients with myocardial infarction (MI). Bone marrow-derived hMSCs may ameliorate consequences of MI, and have the advantages of preparation ease, allogeneic use due to immunoprivilege, capacity to home to injured tissue, and extensive pre-clinical support. We performed a double-blind, placebo-controlled, dose-ranging (0.5, 1.6, and 5 million cells/kg) safety trial of intravenous allogeneic hMSCs (Prochymal, Osiris Therapeutics, Inc., Baltimore, Maryland) in reperfused MI patients (n = 53). The primary end point was incidence of treatment-emergent adverse events within 6 months. Ejection fraction and left ventricular volumes determined by echocardiography and magnetic resonance imaging were exploratory efficacy end points. Adverse event rates were similar between the hMSC-treated (5.3 per patient) and placebo-treated (7.0 per patient) groups, and renal, hepatic, and hematologic laboratory indexes were not different. Ambulatory electrocardiogram monitoring demonstrated reduced ventricular tachycardia episodes (p = 0.025), and pulmonary function testing demonstrated improved forced expiratory volume in 1 s (p = 0.003) in the hMSC-treated patients. Global symptom score in all patients (p = 0.027) and ejection fraction in the important subset of anterior MI patients were both significantly better in hMSCs versus placebo subjects. In the cardiac magnetic resonance imaging substudy, hMSC treatment, but not placebo, increased left ventricular ejection fraction and led to reverse remodeling. Intravenous allogeneic hMSCs are safe in patients after acute MI. This trial provides pivotal safety and provisional efficacy data for an allogeneic bone marrow-derived stem cell in post-infarction patients. (Safety Study of Adult Mesenchymal Stem Cells [MSC] to Treat Acute Myocardial Infarction; NCT00114452)
登录
查看更多内容
影响因子：
37.8
作者：
Anversa, P;Kajstura, J;Bolli, R
通讯作者：
Bolli, R
影响因子：
4.8
作者：
Koç, ON;Day, J;Krivit, W
通讯作者：
Krivit, W
影响因子：
39.3
作者：
Freyman, T;Polin, G;Wilensky, RL
通讯作者：
Wilensky, RL
影响因子：
5.2
作者：
Gnecchi, Massimiliano;He, Huamei;Melo, Luis G.;Noiseaux, Nicolas;Morello, Fulvio;de Boer, Rudolf A.;Zhang, Lunan;Pratt, Richard E.;Dzau, Victor J.;Ingwall, Joanne S.
通讯作者：
Ingwall, Joanne S.
影响因子：
39.3
作者：
Bartunek, Jozef;Dimmeler, Stephanie;Zeiher, Andreas
通讯作者：
Zeiher, Andreas