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Preliminary Communication
ONLINE FIRST
November 5, 2012

Comparison of Allogeneic vs Autologous Bone Marrow–Derived Mesenchymal Stem Cells Delivered by Transendocardial Injection in Patients With Ischemic Cardiomyopathy: The POSEIDON Randomized Trial

Author Affiliations

Author Affiliations: The Interdisciplinary Stem Cell Institute (Drs Hare, Zambrano, Suncion, Schulman, Da Silva, McNiece, and Heldman and Ms DiFede Velazquez), Departments of Medicine (Drs Hare, Zambrano, Tracy, Schulman, Byrnes, Lowery, McNiece, and Heldman), Radiology (Drs Fishman and Ghersin), and Surgery (Dr Ruiz and Ms Amador), University of Miami Miller School of Medicine, Miami, Florida; Cardiovascular Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland (Drs Gerstenblith, Johnston, Brinker, George, and Lardo and Mss Breton and Davis-Sproul); Miami Veterans Affairs Healthcare System, Miami, Florida (Dr Schulman); EMMES Corporation, Rockville, Maryland (Mr Mendizabal); and Biocardia Inc, San Carlos, California (Drs Rouy, Altman, and Wong Po Foo). Dr McNiece is now with the Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston.

JAMA. 2012;308(22):2369-2379. doi:10.1001/jama.2012.25321
Abstract

Context Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared.

Objective To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM.

Design, Setting, and Patients A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up.

Intervention Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites.

Main Outcome Measures Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs). Efficacy assessments included 6-minute walk test, exercise peak VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index.

Results Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%. The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46). At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10). Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO2 max. Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P < .001) and sphericity index but did not increase EF. Allogeneic MSCs reduced LV end-diastolic volumes. Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF. Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions.

Conclusions In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling.

Trial Registration clinicaltrials.gov Identifier: NCT01087996

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