A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study of Intravenous Adult Human Mesenchymal Stem Cells (Prochymal) After Acute Myocardial Infarction

被引:999
作者
Hare, Joshua M. [1 ,2 ]
Traverse, Jay H. [3 ]
Henry, Timothy D. [3 ]
Dib, Nabil [4 ]
Strumpf, Robert K. [4 ]
Schulman, Steven P. [5 ]
Gerstenblith, Gary [5 ]
DeMaria, Anthony N. [6 ]
Denktas, Ali E. [7 ]
Gammon, Roger S. [8 ]
Hermiller, James B., Jr. [9 ]
Reisman, Mark A. [10 ]
Schaer, Gary L. [11 ]
Sherman, Warren [12 ]
机构
[1] Univ Miami, Dept Med, Div Cardiovasc, Miami, FL USA
[2] Univ Miami, Miller Sch Med, Interdisciplinary Stem Cell Inst, Miami, FL 33136 USA
[3] Minneapolis Heart Inst, Minneapolis, MN USA
[4] Arizona Heart Inst, Phoenix, AZ USA
[5] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA
[6] Univ Calif San Diego, San Diego, CA 92103 USA
[7] Univ Texas Houston Med Sch, Houston, TX USA
[8] Heart Hosp Austin, Austin, TX USA
[9] Care Grp LLC, Indianapolis, IN USA
[10] Swedish Med Ctr, Seattle, WA USA
[11] Rush Univ, Med Ctr, Chicago, IL 60612 USA
[12] New York Presbyterian Hosp, New York, NY USA
基金
美国国家卫生研究院;
关键词
magnetic resonance imaging; echocardiography; allogeneic; mesenchymal stem cells; CARDIAC REPAIR; THERAPY; TRANSPLANTATION; REGENERATION; PHENOTYPE; INJECTION; SURVIVAL; TERM; AKT;
D O I
10.1016/j.jacc.2009.06.055
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives Our aim was to investigate the safety and efficacy of intravenous allogeneic human mesenchymal stem cells (hMSCs) in patients with myocardial infarction (MI). Background 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. Methods 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. Results 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. Conclusions 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) (J Am Coll Cardiol 2009;54:2277-86) (C) 2009 by the American College of Cardiology Foundation
引用
收藏
页码:2277 / 2286
页数:10
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