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

Joshua M. Hare, Jay H. Traverse, Timothy D. Henry, Nabil Dib, Robert K. Strumpf, Steven P. Schulman, Gary Gerstenblith, Anthony N. DeMaria, Ali E. Denktas, Roger S. Gammon, James B. Hermiller, Mark A. Reisman, Gary L. Schaer, Warren Sherman

Research output: Contribution to journalArticle

987 Scopus citations

Abstract

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).

Original languageEnglish (US)
Pages (from-to)2277-2286
Number of pages10
JournalJournal of the American College of Cardiology
Volume54
Issue number24
DOIs
StatePublished - Dec 8 2009

Keywords

  • allogeneic
  • echocardiography
  • magnetic resonance imaging
  • mesenchymal stem cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Hare, J. M., Traverse, J. H., Henry, T. D., Dib, N., Strumpf, R. K., Schulman, S. P., Gerstenblith, G., DeMaria, A. N., Denktas, A. E., Gammon, R. S., Hermiller, J. B., Reisman, M. A., Schaer, G. L., & Sherman, W. (2009). A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study of Intravenous Adult Human Mesenchymal Stem Cells (Prochymal) After Acute Myocardial Infarction. Journal of the American College of Cardiology, 54(24), 2277-2286. https://doi.org/10.1016/j.jacc.2009.06.055