TY - JOUR
T1 - Safety and efficacy of the intravenous infusion of umbilical cord mesenchymal stem cells in patients with heart failure
T2 - 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
N1 - Funding Information:
This study was supported by a grant from the Chilean Economic Development Agency (CORFO 11IEI-9766).
Publisher Copyright:
© 2017 The Authors.
PY - 2017
Y1 - 2017
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.
AB - 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.
KW - Cardiomyopathies
KW - Clinical trial
KW - Heart failure
KW - Mesenchymal stromal cells
KW - Umbilical cord
UR - http://www.scopus.com/inward/record.url?scp=85032618937&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.117.310712
DO - 10.1161/CIRCRESAHA.117.310712
M3 - Article
C2 - 28974553
AN - SCOPUS:85032618937
SN - 0009-7330
VL - 121
SP - 1192
EP - 1204
JO - Circulation Research
JF - Circulation Research
IS - 10
ER -