Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy

作者：Joshua M. Hare, Darcy L. DiFede, Angela C. Rieger, Victoria Florea, Ana Marie Landin, Jill El-Khorazaty, Aisha Khan, Muzammil Mushtaq, Maureen H. Lowery, John Byrnes, Robert C. Hendel, Mauricio G. Cohen, Carlos E. Alfonso, Krystalenia Valasaki, Marietsy V. Pujol, Samuel Golpanian, Eduard Ghersin, Joel E. Fishman, Pradip M. Pattany, Samirah Abreu Gomes, Cindy Delgado, Roberto Miki, Fouad Abuzeid, Mayra Vidro-Casiano, Courtney Premer, Audrey Medina, Valeria Porras, Konstantinos E. Hatzistergos, Erica Anderson, Adam Mendizabal, Raul D. Mitrani, Alan W. Heldman · 发表于：Journal of the American College of Cardiology · 年份：2016 · DOI：10.1016/j.jacc.2016.11.009 · 被引用次数：357 · 研究领域：Mesenchymal stem cell research、Muscle Physiology and Disorders、Tissue Engineering and Regenerative Medicine

BACKGROUND: Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic nonischemic dilated cardiomyopathy (NIDCM). OBJECTIVES: 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). M...