Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial

Javed Butler, Stephen E. Epstein, Stephen J. Greene, Arshed A. Quyyumi, Sergey Sikora, Raymond J. Kim, Allen S. Anderson, Jane E. Wilcox, Nikolai I. Tankovich, Michael J. Lipinski, Yi An Ko, Kenneth B. Margulies, Robert T. Cole, Hal A. Skopicki, Mihai Gheorghiade

Research output: Contribution to journalArticlepeer-review

121 Scopus citations


Rationale: Potential benefits of mesenchymal stem cell (MSC) therapy in heart failure may be related to paracrine properties and systemic effects, including anti-inflammatory activities. If this hypothesis is valid, intravenous administration of MSCs should improve outcomes in heart failure, an entity in which excessive chronic inflammation may play a pivotal role. Objective: To assess the safety and preliminary efficacy of intravenously administered ischemia-tolerant MSCs (itMSCs) in patients with nonischemic cardiomyopathy. Methods and Results: This was a single-blind, placebo-controlled, crossover, randomized phase II-a trial of nonischemic cardiomyopathy patients with left ventricular ejection fraction ≤40% and absent hyperenhancement on cardiac magnetic resonance imaging. Patients were randomized to intravenously administered itMSCs (1.5×10 6 cells/kg) or placebo; at 90 days, each group received the alternative treatment. Overall, 22 patients were randomized to itMSC (n=10) and placebo (n=12) at baseline. After crossover, data were available for 22 itMSC patients. No major differences in death, hospitalization, or serious adverse events were noted between the 2 treatments. Change from baseline in left ventricular ejection fraction and ventricular volumes was not significantly different between therapies. Compared with placebo, itMSC therapy increased 6-minute walk distance (+36.47 m, 95% confidence interval 5.98-66.97; P=0.02) and improved Kansas City Cardiomyopathy clinical summary (+5.22, 95% confidence interval 0.70-9.74; P=0.02) and functional status scores (+5.65, 95% confidence interval -0.11 to 11.41; P=0.06). The data demonstrated MSC-induced immunomodulatory effects, the magnitude of which correlated with improvement in left ventricular ejection fraction. Conclusions: In this pilot study of patients with nonischemic cardiomyopathy, itMSC therapy was safe, caused immunomodulatory effects, and was associated with improvements in health status and functional capacity.

Original languageEnglish (US)
Pages (from-to)332-340
Number of pages9
JournalCirculation research
Issue number2
StatePublished - Jan 20 2017
Externally publishedYes


  • cardiomyopathy
  • clinical trial
  • heart failure
  • noni
  • schemic
  • stem cells
  • viable myocardium

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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