• Jorge Bartolucci, Fernando J Verdugo, Paz L González, Ricardo E Larrea, Ema Abarzua, Carlos Goset, Pamela Rojo, Ivan Palma, Ruben Lamich, Pablo A Pedreros, Gloria Valdivia, Valentina M Lopez, Carolina Nazzal, Francisca Alcayaga-Miranda, Jimena Cuenca, Matthew J Brobeck, Amit N Patel, Fernando E Figueroa, and Maroun Khoury.
• From the Laboratory of Nano-Regenerative Medicine (J.B., P.L.G., F.A.-M., J.C., F.E.F., M.K.) and Department of Internal Medicine (F.J.V., R.E.L., F.E.F.), Faculty of Medicine, Universidad de los Andes, Santiago, Chile; Department of Cardiology, Clínica Santa Maria, Santiago, Chile (J.B., E.A., C.G., R.L., P.A.P., G.V.); Program for Translational Research in Cell Therapy, Clínica Universidad de los Andes, Santiago, Chile (J.B., F.J.V., F.E.F., M.K.); Consorcio Regenero, Chilean Consortium for Regenerative Medicine, Santiago, Chile (P.L.G., F.A., J.C., F.E.F., M.K.); Department of Cardiology, Clínica Davila, Santiago, Chile (R.E.L., P.R., I.P.); Cells for Cells, Santiago, Chile (V.M.L., M.K.); Public Health School, Faculty of Medicine, Universidad de Chile, Santiago, Chile (C.N.); Division of Physical Medicine Rehabilitation, University of Utah, Salt Lake City (M.J.B.); and Department of Surgery, University of Miami School of Medicine, FL (A.N.P.).
• Circ. Res. 2017 Oct 27; 121 (10): 1192-1204.

RationaleUmbilical cord-derived mesenchymal stem cells (UC-MSC) are easily accessible and expanded in vitro, possess distinct properties, and improve myocardial remodeling and function in experimental models of cardiovascular disease. Although bone marrow-derived mesenchymal stem cells have been previously assessed for their therapeutic potential in individuals with heart failure and reduced ejection fraction, no clinical trial has evaluated intravenous infusion of UC-MSCs in these patients.ObjectiveEvaluate the safety and efficacy of the intravenous infusion of UC-MSC in patients with chronic stable heart failure and reduced ejection fraction.Methods And ResultsPatients with heart failure and reduced ejection fraction under optimal medical treatment were randomized to intravenous infusion of allogenic UC-MSCs (Cellistem, Cells for Cells S.A., Santiago, Chile; 1×106 cells/kg) or placebo (n=15 per group). UC-MSCs in vitro, compared with bone marrow-derived mesenchymal stem cells, displayed a 55-fold increase in the expression of hepatocyte growth factor, known to be involved in myogenesis, cell migration, and immunoregulation. UC-MSC-treated patients presented no adverse events related to the cell infusion, and none of the patients tested at 0, 15, and 90 days presented alloantibodies to the UC-MSCs (n=7). Only the UC-MSC-treated group exhibited significant improvements in left ventricular ejection fraction at 3, 6, and 12 months of follow-up assessed both through transthoracic echocardiography (P=0.0167 versus baseline) and cardiac MRI (P=0.025 versus baseline). Echocardiographic left ventricular ejection fraction change from baseline to month 12 differed significantly between groups (+7.07±6.22% versus +1.85±5.60%; P=0.028). In addition, at all follow-up time points, UC-MSC-treated patients displayed improvements of New York Heart Association functional class (P=0.0167 versus baseline) and Minnesota Living with Heart Failure Questionnaire (P<0.05 versus baseline). At study completion, groups did not differ in mortality, heart failure admissions, arrhythmias, or incident malignancy.ConclusionsIntravenous infusion of UC-MSC was safe in this group of patients with stable heart failure and reduced ejection fraction under optimal medical treatment. Improvements in left ventricular function, functional status, and quality of life were observed in patients treated with UC-MSCs.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov/ct2/show/NCT01739777. Unique identifier: NCT01739777.© 2017 The Authors.

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