Table 1.

Clinical trials investigating mesenchymal stem cells in heart failure.

Study name	Trial	Phase	Results	Trial identifier	Citation
Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial (POSEIDON)	To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM	Phase 1/2 randomized	Patients with ICM that received transendocardial injection of allogeneic and autologous MSCs demonstrated favorable outcomes on patient functional capacity, quality of life, and ventricular remodeling without adverse effects	NCT01087996	[32]
Cardiopoietic stem cell therapy in heart failure: the C-CURE (cardiopoietic stem cell therapy in heart failure) multicenter randomized trial with lineage-specified biologics (C-CURE)	To evaluate the feasibility and safety of autologous bone marrow-derived and cardiogenically oriented mesenchymal stem cell therapy and to probe for signs of efficacy in patients with chronic heart failure	Prospective, multicenter, randomized trial	Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in chronic heart failure, meriting definitive clinical evaluation	NCT00810238	[67]
Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial (TAC-HFT)	To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells (MSCs) and bone marrow mononuclear cells in patients with ischemic cardiomyopathy	Phase 1 and 2 randomized, blinded, placebo-controlledstudy	Transendocardial stem cell injection with MSCs or bone marrow mononuclear cells appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction	NCT00768066	[73]
Rationale and design of the first randomized, double-blind, placebo-controlled trial of intramyocardial injection of autologous bone-marrow derived mesenchymal stromal cells in chronic ischemic heart failure (MSC-HF Trial) (MSC-HF)	To investigate the role of MSCs in patients with chronic ischemia utilizing intramyocardial injections in an ischemic viable region of the myocardium using the electromechanical NOGA-XP system	Phase 2, single-center, double-blind, randomized, placebo-controlledtrial	Intramyocardial injection of bone marrow-derived MSCs decreased LVEV, improved LV EF, increased stroke volume, and increased myocardial mass significantly compared to placebo	NCT00644410	[76]
A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF) (FOCUS-HF)	To evaluate the safety and efficacy of the transendocardial delivery of autologous bone marrow mononuclear cells in patients with chronic HF	Phase 1, single-blind trial	Autologous bone marrow mononuclear cell therapy is safe and improves symptoms, quality of life, and possibly perfusion in patients with chronic HF	NCT00203203	[69]
RIMECARD	To assess the safety and efficacy of umbilical cord-derived MSCs in compensated dilated CM	Phase 1/2	Completed	NCT01739777
TEVA CEP-41750 (DREAM-HF)	To evaluate efficacy and safety of allogeneic mesenchymal precursor cells (CEP-41750) for the treatment of chronic HF	Phase 3	Ongoing	NCT02032004
Combination of mesenchymal and C-kit+ cardiac stem cells as regenerative therapy for heart failure (CONCERT-HF)	To evaluate the feasibility, safety, and effect of MSCs CSCs, and combination in heart failure of ischemic etiology, administered by transendocardial injection in ischemic cardiomyopathy	Phase 2 randomized, placebo-controlledclinical trial	Ongoing	NCT02501811
Intravenous administration of allogeneic bone marrow-derived multipotent mesenchymal stromal cells (MSCs) in patients with recent onset anthracycline-associated cardiomyopathy	To learn if adding mesenchymal stem cells (MSCs) to standard-of-care drugs can help control heart failure that may have been caused by anthracyclines	Phase 1	Ongoing	NCT02408432
Intravenous allogeneic mesenchymal stem cells for nonischemic cardiomyopathy: safety and efficacy results of a phase II-A randomized trial	To assess the safety and preliminary efficacy of intravenously administered ischemia-tolerant MSCs (itMSCs) in patients with nonischemic cardiomyopathy	Phase 2 single-blind, placebo-controlled, crossover, randomized	In patients with nonischemic cardiomyopathy, ischemia-tolerant MSC therapy was safe, caused immunomodulatory effects, and was associated with improvements in health status and functional capacity	NCT02467387	[72]
A randomized clinical trial of adipose-derived stem & regenerative cells in the treatment of patients with non revascularizable ischemic myocardium – the PRECISE trial (PRECISE)	To establish safety and feasibility of utilizing adipose derived stem & regenerative cells (ADRCs) in patients who have areas of myocardium that are not revascularizable and have demonstrated reversible ischemia	Phase 1, randomized, double-blind trial	Isolation and transendocardial injection of autologous ADRCs in no-option patients were safe and feasible	NCT00426868
Allogeneic adipose tissue-derived stromal/stem cell therapy in patients with ischemic heart disease and heart failure - a safety study	To perform a small clinical safety trial in heart failure patients with allogeneic adipose tissue-derived mesenchymal stem cells	Phase 1	Ongoing	NCT02387723 2015-001560-19
Stem cell therapy in ischemic non-treatable cardiac disease - SCIENCE A European Multi-Centre Trial (SCIENCE)	To investigate the efficacy of direct intramyocardial injection allogeneic adipose-derived stem cells in patients with reduced left ventricular ejection fraction (EF) (≤45%) and heart failure	Phase 2, double-blind, placebo-controlledtrial	Ongoing	NCT02673164 2015-002929-19
Efficacy and safety of bone marrow-derived mesenchymal cardiopoietic cells (C3BS-CQR-1) for the treatment of chronic advanced ischemic heart failure (CHART-1)	To evaluate the safety and efficacy of C3BS-CQR-1 by comparing the overall response to standard of care and C3BS-CQR-1 relative to standard of care and a sham procedure	Phase 3, randomized, double-blind trial	Ongoing	NCT01768702