Table 1.
Clinical efficacy of MSC therapy: data from clinical trials
| Clinical trials | Design | Type of cells, dose, and delivery route | Studied population | Follow-up (months) | Results |
|---|---|---|---|---|---|
| Rationale and design of the first randomized, double-blind, placebo-controlled trial of intra-myocardial injection of autologous bone-marrow-derived mesenchymal stromal cells in chronic ischemic heart failure (MSC-HF Trial) [12]. | Phase II, single-center, double-blind, randomized, placebo-controlled trial. |
- Autologous bone-marrow-derived MSCs. - 12 to 15 injections, of each 0.2 mL stem cell solution or placebo. - Intra-myocardial injection |
60 patients with chronic ischemic heart failure randomized in a 2:1. | 12 | Significant improvements in left ventricular systolic function (↑LVESV, LVEF, SV, and cardiac output) |
| Intra-myocardial transplantation of mesenchymal stromal cells for chronic myocardial ischemia and impaired left ventricular function: Results of the MESAMI 1 pilot trial [6]. | Bicentric pilot study |
- Autologous bone marrow-derived mesenchymal stromal cells. - Mean of 61.5 × 106 cells per patient - Intra-myocardial injection |
10 patients with chronic myocardial ischemia, LVEF ≤ 35%, and reversible perfusion defects | 24 | Safety of MSC therapy with potential improvement in cardiac performance, left ventricular remodeling, and clinically functional status. |
| Intra-myocardial injection of mesenchymal precursor cells and successful temporary weaning from left ventricular assist device support in patients with advanced heart failure: a randomized clinical trial [16]. | Randomized phase 2 clinical trial |
- Allogenic mesenchymal precursor cells - 150 million cells - Intra-myocardial injection |
159 with end-stage heart failure | 12 |
- No improvement in left ventricular recovery - Higher dose producing the greatest improvement in cardiac structure and function |
| Dose comparison study of allogeneic mesenchymal stem cells in patients with ischemic cardiomyopathy (The TRIDENT Study) [17]. | Double-blind randomized clinical trials |
- Allogenic bone marrow-derived human MSCs - 20 million versus 100 million cells. - Trans-endocardial injection |
30 patients with ischemic cardiomyopathy. | 6 | Both doses reduced scar size while only high dose increases |
| A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction [18]. | Double-blind, randomized, placebo-controlled trial. |
- Allogenic mesenchymal stem cells - Dose-ranging (0.5, 1.6, and 5 million cells/kg) - Intravenous administration |
53 patients presenting for first myocardial infarction between 1 to 10 days before randomization. | 6 | Safety of intravenous administration of MSCs after acute myocardial infarction. |
| Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist device [19] | Multicenter, double-blind, sham-procedure controlled trial |
- Allogenic MPCs. - 25 million of cells injected during left ventricular assist device implantation. - Intra-myocardial injection |
30 patients with end-stage heart failure planned to LVAD implantation were randomized 2:1 | 12 | Administration of MPCs appeared to be safe, and there was a potential signal of efficacy |
| Intravenous allogenic mesenchymal stem cells for nonischemic cardiomyopathy: safety and efficacy results of a phase ii-a randomized trial [20]. | Single-blind, placebo-controlled, crossover, randomized phase II-a trial |
- Mesenchymal stem cells - 1.5 × 106 cells/kg - Intravenous administration |
22 patients with non-ischemic cardiomyopathy with left ventricular ejection fraction. | 3 | MSC therapy was safe, caused immunomodulatory effects, and was associated with improvements in health status and functional capacity. |
| Randomized, double-blind, phase I/II study of intravenous allogenic mesenchymal stromal cells in acute myocardial infarction [21]. | A phase I/II randomized, double-blind, single-dose study. |
- Bone marrow-derived allogenic MSCs (Stempeucel). - 2 million cells/kg - Intravenous |
20 patients who had undergone percutaneous coronary intervention for STEMI were randomly assigned (1:1) | 24 | Stempeucel was safe and well-tolerated when administered intravenously in AMI patients 2 days after percutaneous coronary intervention |
| Adipose-derived regenerative cells in patients with ischemic cardiomyopathy: the PRECISE Trial [22]. | Randomized, placebo-controlled, double-blind trial. |
- ADRCs. - 3 escalating doses 0.4×106 ADRCs/kg, 0.8×106 ADRCs/kg, and 1.2×106 ADRCs/kg. -Transendocardial injections. |
21 ADRC-treated and 6 control patients with ischemic cardiomyopathy. | 36 |
- Isolation and trans-endocardial injection of autologous ADRCs in no-option patients were safe and feasible. - ADRCs preserve ventricular function, myocardial perfusion, and exercise capacity. |
| 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) [23]. | Phase 1/2, randomized, double-blind, placebo-controlled clinical trial. |
- Allogenic UC-MSCs (Cellistem, Cells for Cells S.A., Santiago, Chile). - 1 × 106 cells/kg - Intravenous infusion |
30 patients with heart failure and reduced ejection fraction under optimal medical treatment. | 12 |
- Intravenous infusion of UC-MSCs was safe. - Improvements in left ventricular function, functional status, and quality of life. |
| Adipose-derived stromal cells for treatment of patients with chronic ischemic heart disease (my stromalcell trial): a randomized placebo-controlled study [24]. | Randomized double-blind placebo-controlled. |
- ADSCs from the abdomen were culture expanded and stimulated with VEGF-A165. - 10–15 injections of 0.2 mL of ASCs. - A NOGA Myostar® catheter was used for intra-myocardial cells delivery. |
60 patients with CCS/NYHA class II-III, left ventricular ejection fraction > 40%, and at least one significant coronary artery stenosis | 6 | - ADSCs treatment was safe but did not improve exercise capacity compared to placebo. |
| Cardiopoietic stem cell therapy in heart failure: the C-CURE (cardiopoietic stem cell therapy in heart failure) multicenter randomized trial with lineage-specified biologics [25]. | A prospective, multicenter, randomized trial. |
- Pre-treated MSCs with cardiogenic cocktail. - An average of 18 injections per patient. - Endo-ventricular injection using the NOGA. |
48 patients with stable heart failure (15–40%) and a history of myocardial infarction. | 24 | - Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in chronic HF. |
| Bone marrow-derived mesenchymal stromal cell treatment in patients with severe ischaemic heart failure: a randomized placebo-controlled trial (MSC-HF trial) [26]. | Randomized, double-blind, placebo-controlled trial. |
- Autologous bone marrow-derived mesenchymal stromal cells. - 10 to 15 injections of 0.2 mL. - Intra-myocardial injection. |
60 patients with ischemic heart failure were randomized 2:1 | 6 | -Intra-myocardial injection of autologous MSCs was safe and improved myocardial function in patients with severe ischemic HF. |
| Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double-blind, sham-controlled CHART-1 clinical trial [27]. | Large randomized, double-blind, sham-controlled multicentric study. |
- Autologous cardiopoietic stem cells. - 60 million cells - Intra-myocardial injection |
240 patients with chronic HF secondary to ischemic heart disease, reduced LVEF (< 35%), and at high risk for recurrent HF-related events despite optimal medical therapy. | 24 | Efficacy and safety of autologous cardiopoietic stem cells in the treatment of chronic ischemic HF. |
| Comparison of allogenic vs autologous bone marrow-derived mesenchymal stem cells delivered by trans-endocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial [11]. | Phase 1/2 randomized comparative trial. |
- Autologous versus allogenic MSCs. - 20 million, 100 million, or 200 million cells (5 patients in each cell type per dose level). - Trans-endocardial injection |
30 patients with left ventricular dysfunction due to ischemic cardiomyopathy | 12 | - MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling. |
| Trans-endocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial [28]. | A phase 1 and 2 randomized, blinded, placebo-controlled trial. |
- MSCs and bone marrow mononuclear cells. - 10 injections. - Trans-endocardial administration. |
65 patients with ischemic cardiomyopathy and LVEF less than 50% [MSCs (n = 19) with placebo (n = 11) and BMCs (n = 19) with placebo (n = 10)]. | 12 | Trans-endocardial stem cell injection with MSCs or BMCs appeared to be safe for patients with chronic ischemic cardiomyopathy and left ventricular dysfunction. |
ADRCs adipose-derived regenerative cells, ADSCs adipose-derived stromal cells, BMCs bone-marrow mononucleated cells, CCS Canadian Cardiovascular Society, HF heart failure, LVAD left ventricular assist device, LVEF left ventricular ejection fraction, LVESV left ventricular end-systolic volume, MPCs mesenchymal precursor cells, MSCs mesenchymal stem cells, NYHA New York Heart Association, STEMI ST-elevation myocardial infarction, SV systolic volume, UC-MSCs umbilical cord-derived mesenchymal stem cells