Circ Res. 2017 Oct 27;121(10):1192-1204.

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]).

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,† Maroun Khoury† *These authors contributed equally to this article. †These authors contributed equally to this article as co-senior authors.



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.


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


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.


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.




Cellular therapy has been evaluated in cardiovascular diseases for more than a decade without reaching consensus regarding their effect1. Optimal cell source has been a matter of debate, since trials using autologous patient derived BM-MSCs have suggested positive results2, but allogenic cell sources seem superior to autologous MSCs3,4. This is particularly the case in the aged Heart failure patient population, usually with additional comorbid disease5.

In this regard our trial is of interest since it is the first clinical survey of UC-MSCs. This allogenic “juvenile” cell source is easily accessible and we have contributed to its extensive biological and functional characterization6. Indeed, we found that these cells exhibit superior angiogenic and paracrine effects and also migratory capacity when compared with BM-MSCs6. Furthermore, there is ample clinical experience and follow-up7, even in patients with extensive multisystemic disease8, that is coincident with our data, showing no significant adverse effects.

Finally the advantages of a simple intravenous infusion, as opposed to more invasive forms of intramyocardial local implantation, should also be stressed, as did the accompanying Editorial article of Circulation Research, titled: Cardiac Cell Therapy Evolving From Complex to Straightforward Enabling Adoption and Affordability9

Indeed, this “straightforward… affordability” is the consequence of a procedure that can be carried out as an outpatient procedure, decreasing hospital costs, with no need for invasive procedures, critical care units, high cost implantation catheters, etc. The procedure is open to quick accessibility, given the allogenic nature of cells, apt for cryopreservation and immediate (off-the-shelf), eventually repeated usage.

Cell infusion can be done in ambulatory or day care admission (3-4 hr.), with usual monitorization, by peripheral vein,  manually or by infusion pump. The total cost in our environment is equivalent to US $ 2285, including admission, supplies and cells.



A schematic diagram





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