title: Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy: POSEIDON-DCM Trial.
abstract: BACKGROUND
  Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic nonischemic dilated cardiomyopathy (NIDCM).
  
  
  OBJECTIVE
  The authors conducted a randomized comparison of safety and efficacy of autologous (auto) versus allogeneic (allo) bone marrow-derived hMSCs in NIDCM.
  
  
  METHODS
  Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients received hMSCs (100 million) by transendocardial stem cell injection in 10 left ventricular sites. Treated patients were evaluated at baseline, 30 days, and 3-, 6-, and 12-months for safety (serious adverse events [SAE]), and efficacy endpoints: ejection fraction, Minnesota Living with Heart Failure Questionnaire, 6-min walk test, major adverse cardiac events, and immune biomarkers.
  
  
  RESULTS
  There were no 30-day treatment-emergent SAEs. Twelve-month SAE incidence was 28.2% with allo-hMSCs versus 63.5% with auto-hMSCs (p = 0.1004 for the comparison). One allo-hMSC patient developed an elevated (>80) donor-specific calculated panel reactive antibody level. The ejection fraction increased in allo-hMSC patients by 8.0 percentage points (p = 0.004) compared with 5.4 with auto-hMSCs (p = 0.116; allo vs. auto p = 0.4887). The 6-min walk test increased with allo-hMSCs by 37.0 m (p = 0.04), but not auto-hMSCs at 7.3 m (p = 0.71; auto vs. allo p = 0.0168). MLHFQ score decreased in allo-hMSC (p = 0.0022) and auto-hMSC patients (p = 0.463; auto vs. allo p = 0.172). The major adverse cardiac event rate was lower, too, in the allo group (p = 0.0186 vs. auto). Tumor necrosis factor-α decreased (p = 0.0001 for each), to a greater extent with allo-hMSCs versus auto-hMSCs at 6 months (p = 0.05).
  
  
  CONCLUSIONS
  These findings demonstrated safety and clinically meaningful efficacy of allo-hMSC versus auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are warranted based on these results. (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy [PoseidonDCM]; NCT01392625).
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida; Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida. Electronic address: JHare@med.miami.edu.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Darcy L
authors.initials: DL
authors.lastname: DiFede
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Rieger
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Victoria
authors.initials: V
authors.lastname: Florea
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Landin
authors.affiliation: The Emmes Corporation, Rockville, Maryland.
authors.forename: Jill
authors.initials: J
authors.lastname: El-Khorazaty
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Aisha
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Muzammil
authors.initials: M
authors.lastname: Mushtaq
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Maureen H
authors.initials: MH
authors.lastname: Lowery
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: John J
authors.initials: JJ
authors.lastname: Byrnes
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hendel
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Mauricio G
authors.initials: MG
authors.lastname: Cohen
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Alfonso
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Krystalenia
authors.initials: K
authors.lastname: Valasaki
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Marietsy V
authors.initials: MV
authors.lastname: Pujol
authors.affiliation: Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Samuel
authors.initials: S
authors.lastname: Golpanian
authors.affiliation: Department of Radiology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Eduard
authors.initials: E
authors.lastname: Ghersin
authors.affiliation: Department of Radiology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Joel E
authors.initials: JE
authors.lastname: Fishman
authors.affiliation: Department of Radiology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Pradip
authors.initials: P
authors.lastname: Pattany
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Samirah A
authors.initials: SA
authors.lastname: Gomes
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Cindy
authors.initials: C
authors.lastname: Delgado
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Roberto
authors.initials: R
authors.lastname: Miki
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Fouad
authors.initials: F
authors.lastname: Abuzeid
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Mayra
authors.initials: M
authors.lastname: Vidro-Casiano
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Courtney
authors.initials: C
authors.lastname: Premer
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Audrey
authors.initials: A
authors.lastname: Medina
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Valeria
authors.initials: V
authors.lastname: Porras
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Konstantinos E
authors.initials: KE
authors.lastname: Hatzistergos
authors.affiliation: The Emmes Corporation, Rockville, Maryland.
authors.forename: Erica
authors.initials: E
authors.lastname: Anderson
authors.affiliation: The Emmes Corporation, Rockville, Maryland.
authors.forename: Adam
authors.initials: A
authors.lastname: Mendizabal
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Raul
authors.initials: R
authors.lastname: Mitrani
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Heldman
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000601:surgery*; D005260:Female; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D012449:Safety; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: endothelial function; heart failure; idiopathic dilated cardiomyopathy; immune biomarker; stem cell therapy