title: Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01087996.
authors.affiliation: Interdisciplinary Stem Cell Institute, and Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida 33101, USA. jhare@med.miami.edu
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
authors.forename: Joel E
authors.initials: JE
authors.lastname: Fishman
authors.forename: Gary
authors.initials: G
authors.lastname: Gerstenblith
authors.forename: Darcy L
authors.initials: DL
authors.lastname: DiFede Velazquez
authors.forename: Juan P
authors.initials: JP
authors.lastname: Zambrano
authors.forename: Viky Y
authors.initials: VY
authors.lastname: Suncion
authors.forename: Melissa
authors.initials: M
authors.lastname: Tracy
authors.forename: Eduard
authors.initials: E
authors.lastname: Ghersin
authors.forename: Peter V
authors.initials: PV
authors.lastname: Johnston
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Brinker
authors.forename: Elayne
authors.initials: E
authors.lastname: Breton
authors.forename: Janice
authors.initials: J
authors.lastname: Davis-Sproul
authors.forename: Ivonne H
authors.initials: IH
authors.lastname: Schulman
authors.forename: John
authors.initials: J
authors.lastname: Byrnes
authors.forename: Adam M
authors.initials: AM
authors.lastname: Mendizabal
authors.forename: Maureen H
authors.initials: MH
authors.lastname: Lowery
authors.forename: Didier
authors.initials: D
authors.lastname: Rouy
authors.forename: Peter
authors.initials: P
authors.lastname: Altman
authors.forename: Cheryl
authors.initials: C
authors.lastname: Wong Po Foo
authors.forename: Phillip
authors.initials: P
authors.lastname: Ruiz
authors.forename: Alexandra
authors.initials: A
authors.lastname: Amador
authors.forename: Jose
authors.initials: J
authors.lastname: Da Silva
authors.forename: Ian K
authors.initials: IK
authors.lastname: McNiece
authors.forename: Alan W
authors.initials: AW
authors.lastname: Heldman
authors.forename: Richard
authors.initials: R
authors.lastname: George
authors.forename: Albert
authors.initials: A
authors.lastname: Lardo
mesh_terms: D000368:Aged; D016026:Bone Marrow Transplantation / Q000379:methods*; D009202:Cardiomyopathies / Q000628:therapy*; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000628:therapy*; D011788:Quality of Life; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000628:therapy; D020257:Ventricular Remodeling
chemical_list: D006680:HLA Antigens