Author + information
- Received March 17, 2009
- Revision received May 20, 2009
- Accepted June 15, 2009
- Published online December 8, 2009.
- Joshua M. Hare, MD⁎,⁎ (, )
- Jay H. Traverse, MD†,
- Timothy D. Henry, MD†,
- Nabil Dib, MD‡,
- Robert K. Strumpf, MD‡,
- Steven P. Schulman, MD§,
- Gary Gerstenblith, MD§,
- Anthony N. DeMaria, MD∥,
- Ali E. Denktas, MD¶,
- Roger S. Gammon, MD#,
- James B. Hermiller Jr, MD⁎⁎,
- Mark A. Reisman, MD††,
- Gary L. Schaer, MD‡‡ and
- Warren Sherman, MD§§
- ↵⁎Reprint requests and correspondence:
Dr. Joshua M. Hare, Leonard M. Miller School of Medicine, Interdisciplinary Stem Cell Institute and Division of Cardiology, Biomedical Research Building, Room 824, P.O. Box 016960 (R-125), Miami, Florida 33136
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)
The study design was developed by Drs. Hare, Gerstenblith, and Schulman, and revised on the basis of discussions with the sponsor (Osiris Therapeutics, Inc., Baltimore, Maryland). The sponsor had no role in data collection, but participated in data analysis and interpretation. Drs. Hare, Gerstenblith, and Schulman also received support from the Johns Hopkins University School of Medicine General Clinical Research Center and National Institutes of Health Specialized Center for Cell-based Therapy (SCCT) grant U54 HL081028. Dr. DeMaria has received research funding/grants from Lantheus, Acusphere, CV Therapeutics, Cardiovascular Biotherapeutics, Angioblast Systems, Inc., Philips Medical Systems, and General Electric Medical Systems; and he has equity interests/stock options in Cardionet. Dr. Hermiller has served as a consultant for BSC. Stephen G. Ellis, MD, served as Guest Editor for this article.
- Received March 17, 2009.
- Revision received May 20, 2009.
- Accepted June 15, 2009.
- American College of Cardiology Foundation