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Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]).
Circ Res. 2017 Oct 27; 121(10):1192-1204.CircR

Abstract

RATIONALE

Umbilical 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.

OBJECTIVE

Evaluate the safety and efficacy of the intravenous infusion of UC-MSC in patients with chronic stable heart failure and reduced ejection fraction.

METHODS AND RESULTS

Patients 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.

CONCLUSIONS

Intravenous 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 REGISTRATION

URL: https://www.clinicaltrials.gov/ct2/show/NCT01739777. Unique identifier: NCT01739777.

Authors+Show Affiliations

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.).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.).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.).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.).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.).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.).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.).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.).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.).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.).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.).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.).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.).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.).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.).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.).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.).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.). ffigueroa@uandes.cl.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.).

Pub Type(s)

Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

28974553

Citation

Bartolucci, Jorge, et al. "Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: a Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells On Cardiopathy])." Circulation Research, vol. 121, no. 10, 2017, pp. 1192-1204.
Bartolucci J, Verdugo FJ, González PL, et al. Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]). Circ Res. 2017;121(10):1192-1204.
Bartolucci, J., Verdugo, F. J., González, P. L., Larrea, R. E., Abarzua, E., Goset, C., Rojo, P., Palma, I., Lamich, R., Pedreros, P. A., Valdivia, G., Lopez, V. M., Nazzal, C., Alcayaga-Miranda, F., Cuenca, J., Brobeck, M. J., Patel, A. N., Figueroa, F. E., & Khoury, M. (2017). Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]). Circulation Research, 121(10), 1192-1204. https://doi.org/10.1161/CIRCRESAHA.117.310712
Bartolucci J, et al. Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: a Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells On Cardiopathy]). Circ Res. 2017 Oct 27;121(10):1192-1204. PubMed PMID: 28974553.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]). AU - Bartolucci,Jorge, AU - Verdugo,Fernando J, AU - González,Paz L, AU - Larrea,Ricardo E, AU - Abarzua,Ema, AU - Goset,Carlos, AU - Rojo,Pamela, AU - Palma,Ivan, AU - Lamich,Ruben, AU - Pedreros,Pablo A, AU - Valdivia,Gloria, AU - Lopez,Valentina M, AU - Nazzal,Carolina, AU - Alcayaga-Miranda,Francisca, AU - Cuenca,Jimena, AU - Brobeck,Matthew J, AU - Patel,Amit N, AU - Figueroa,Fernando E, AU - Khoury,Maroun, Y1 - 2017/09/26/ PY - 2017/01/31/received PY - 2017/08/14/revised PY - 2017/08/24/accepted PY - 2017/10/5/pubmed PY - 2017/11/3/medline PY - 2017/10/5/entrez KW - cardiomyopathies KW - clinical trial KW - heart failure KW - mesenchymal stromal cells KW - umbilical cord SP - 1192 EP - 1204 JF - Circulation research JO - Circ. Res. VL - 121 IS - 10 N2 - RATIONALE: Umbilical 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. OBJECTIVE: Evaluate the safety and efficacy of the intravenous infusion of UC-MSC in patients with chronic stable heart failure and reduced ejection fraction. METHODS AND RESULTS: Patients 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. CONCLUSIONS: Intravenous 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 REGISTRATION: URL: https://www.clinicaltrials.gov/ct2/show/NCT01739777. Unique identifier: NCT01739777. SN - 1524-4571 UR - https://www.unboundmedicine.com/medline/citation/28974553/Safety_and_Efficacy_of_the_Intravenous_Infusion_of_Umbilical_Cord_Mesenchymal_Stem_Cells_in_Patients_With_Heart_Failure:_A_Phase_1/2_Randomized_Controlled_Trial__RIMECARD_Trial_[Randomized_Clinical_Trial_of_Intravenous_Infusion_Umbilical_Cord_Mesenchymal_Stem_Cells_on_Cardiopathy]__ L2 - http://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.117.310712?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -