Author + information
- Received October 11, 2016
- Revision received October 26, 2016
- Accepted November 1, 2016
- Published online November 14, 2016.
- Joshua M. Hare, MD1,2,∗ (, )
- Darcy L. DiFede, RN BSN1,
- Angela M. Castellanos, MD MSc1,
- Victoria Florea, MD1,
- Ana M. Landin, PhD1,
- Jill El-Khorazaty, MSc5,
- Aisha Khan, MSc MBA1,
- Muzammil Mushtaq, MD2,
- Maureen H. Lowery, MD2,
- John J. Byrnes, MD2,
- Robert C. Hendel, MD2,
- Mauricio G. Cohen, MD2,
- Carlos E. Alfonso, MD2,
- Krystalenia Valasaki, MSc1,
- Marietsy V. Pujol, MDA1,
- Samuel Golpanian, MD4,
- Eduard Ghersin, MD3,
- Joel E. Fishman, MD PhD3,
- Pradip Pattany, PhD3,
- Samirah A. Gomes, MD PhD1,
- Cindy Delgado, MFA1,
- Roberto Miki, MD2,
- Fouad Abuzeid, MD1,
- Mayra Vidro-Casiano, MPH1,
- Courtney Premer, BSc1,
- Audrey Medina, BSc1,
- Valeria Porras, BSc1,
- Konstantinos E. Hatzistergos, PhD1,
- Erica Anderson, MSc5,
- Adam Mendizabal, PhD5,
- Raul Mitrani, MD2 and
- Alan W. Heldman, MD2
- 1Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida
- 2Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
- 3Department of Radiology, University of Miami Miller School of Medicine, Miami, Florida
- 4Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida
- 5The Emmes Corporation, Rockville, Maryland
- ↵∗Corresponding author: Joshua M. Hare, MD Louis Lemberg Professor of Medicine Director, Interdisciplinary Stem Cell Institute University of Miami Miller School of Medicine Miami, Florida 33136 Telephone: (305) 243-5579 Fax: (305) 243-5584.
Background While human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic non-ischemic dilated cardiomyopathy (NIDCM).
Objectives The POSEIDON-DCM trial is a randomized comparison of safety and efficacy of autologous (auto) vs. 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 (age: 55.8 +11.2; 32% female) received hMSCs (100 million) by transendocardial stem cell injection (TESI) in ten left ventricular sites by NOGA Catheter. Treated patients were evaluated at baseline, 30 days, 3-, 6-, and 12-months for safety: serious adverse events (SAE), and efficacy endpoints: Ejection Fraction (EF), Minnesota Living with Heart Failure Questionnaire (MLHFQ), Six Minute Walk Test (6MWT), MACE, and immune-biomarkers. This trial is registered with ClinicalTrials.gov, #NCT01392625.
Results There were no 30-day treatment-emergent (TE)-SAEs. 12-month SAE incidence was 28.2% (95% CI: 12.8, 55.1) in allo, and 63.5% (95% CI: 40.8, 85.7; p=0.1004) in auto. One allo-group patient developed an elevated donor specific cPRA. EF increased in allo by 8.0 units (95% Cl: 2.8, 13.2; p=0.004), and in auto: 5.4 units (95% Cl: -1.4, 12.1; p=0.116, allo vs. auto p=0.4887). 6MWT increased for allo: 37.0 meters (95% Cl: 2.0 to 72.0; p=0.04), but not auto: 7.3 meters (95% Cl: -47.8, 33.3; p=0.71, auto vs. allo p=0.0168). MLHFQ score decreased in allo (p=0.0022), and auto (p=0.463; p=0.172). The MACE rate was lower in allo vs. auto (p=0.0186). Tumor necrosis factor alpha (TNF-α) decreased (p=0.0001 for each), to a greater extent in allo vs. auto at six-months (p=0.05).
Conclusion These findings demonstrate safety and support greater, clinically meaningful efficacy of allo-hMSC vs. auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are warranted based on these results.
Declaration of Interest: Dr. Hare and Dr. Heldman disclose a relationship with Vestion Inc that includes equity, board membership, and consulting. Dr. Hatzistergos and K. Valasaki disclose a relationship with Vestion Inc that includes equity. Vestion Inc did not participate in funding this work. Dr. Landin, Dr. Hare, A. Khan, and D. DiFede disclose a relationship with Longeveron LLC that includes consulting. Longeveron LLC did not participate in funding this work. D. DiFede discloses a relationship with BDS as consultant. The other authors report no conflicts.
Clinical trial: ClinicalTrials.gov Identifier: NCT01392625 https://clinicaltrials.gov/ct2/show/NCT01392625?term=Hare+%2B+POSEIDON-DCM&rank=1
- Received October 11, 2016.
- Revision received October 26, 2016.
- Accepted November 1, 2016.