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Circ Res. 2017 Jan 20;120(2):332-340. doi: 10.1161/CIRCRESAHA.116.309717. Epub 2016 Nov 16.

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

Author information

1
From the Division of Cardiology, Department of Medicine, Stony Brook University, NY (J.B., H.A.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (S.E.E., M.J.L.); Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (A.A.Q., R.T.C.); CardioCell LLC, San Diego, CA (S.S.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (A.S.A., J.E.W.); Stemedica Cell Technologies Inc, San Diego, CA (N.I.T.); Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA (Y.-A.K.); Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia (K.B.M.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (M.G.). javed.butler@stonybrookmedicine.edu.
2
From the Division of Cardiology, Department of Medicine, Stony Brook University, NY (J.B., H.A.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (S.E.E., M.J.L.); Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (A.A.Q., R.T.C.); CardioCell LLC, San Diego, CA (S.S.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (A.S.A., J.E.W.); Stemedica Cell Technologies Inc, San Diego, CA (N.I.T.); Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA (Y.-A.K.); Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia (K.B.M.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (M.G.).

Abstract

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 (1.5×106 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.

CLINICAL TRIAL REGISTRATION:

URL: http://www.clinicaltrials.gov. Unique identifier: NCT02467387.

KEYWORDS:

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

PMID:
27856497
DOI:
10.1161/CIRCRESAHA.116.309717
[Indexed for MEDLINE]

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