Table 1 Clinical trials utilizing stem cells for the treatment of cardiovascular disorders
From: Tracking of stem cells in vivo for cardiovascular applications
| Trial | Condition | Cell types | Delivery Route | Select Functional Results |
|---|---|---|---|---|
| Strauer et al.[17] | AMI | BMC | Intracoronary | Increase in stroke volume index and ejection fraction. Significant decrease in ESV. Significant increase in the ratio of systolic pressure to end-systolic volume. |
| Kuethe et al.[18] | AMI | BMC | Intracoronary | No improvement of LVEF, regional wall motion at infarcted zone, contractility index, coronary blood flow reserve or maximal oxygen uptake at 3-months. No change in LV EF at 12 months. |
| BOOST [7, 19–21] | AMI | BMC | Intracoronary | Overall treatment effect of BMC transfer on E/A. Significantly lower E/A ratio at 6 and 18 months for control group. No difference in E/A ratio at 60 months between groups. No overall effect of BMC implantation on E(a)/A(a) ratio, DT, IVRT, and E/E(a) ratio. |
| REPAIR-AMI [4, 5] | AMI | BMC or CPCs | Intracoronary | No significant difference in LV volumes between groups, although a trend toward smaller ESVs in the BMC group; significantly improved relative infarct size and regional contractility among BMC recipients. |
| ASTAMI [8, 22] | STEMI | BMC | Intracoronary | No significant differences between groups in change of global LV systolic function at 3 years. Larger improvement in exercise time from 2–3 weeks to 3 years in BMC recipients, but no difference in peak oxygen consumption. |
| REGENT [23] | AMI | Selected (CD34 + CXCR+) BMC, unselected BMC | Intracoronary | Increased LV EF at 6 months in unselected and selected BMC recipients, but unchanged for control group. No significant differences in absolute changes of LV EF between groups. No significant differences in absolute changes of LV ESV and LV EDV for all groups. |
| TECAM [24] | STEMI | BMC | Intracoronary | At 9 months, no significant changes in changes in minimum lumen diameter and the percentage of stenosis at follow-up between BMC and control group; no significant changes in the contralateral artery; and no changes in maximum area stenosis and plaque volume. |
| Hopp et al. (subgroup of ASTAMI) [25] | STEMI | BMC | Intracoronary | For controls, improved global and regional LV function at 6 months versus 2–3 weeks; significantly more than in the BMC group. Significant decrease in LV infarct mass; significantly more pronounced than the BMC group. |
| SWISS-AMI [26] | AMI | BMC | Intracoronary | Intracoronary BMMC did not improve LV function by CMR at 4 months relative to controls whether infused at 5–7 days or 3–4 weeks. Early reperfusion (<4.5 h) after STEMI predictive of more benefit from BMMC. |
| TIME [27, 28] | AMI | BMC | Intracoronary | STEMI patients treated with PCI treated with intracoronary administration of autologous BMCs did not show improved left ventricular function at 6 months or 1 year whether treated at 3 or 7 days after PCI. |
| LateTIME [6] | AMI | BMC | Intracoronary | Delayed (2–3 weeks) intracoronary injection of BMCs does not improve LVEF or regional wall motion or decrease infarct size based on CMR compared to placebo-treated patients. |
| Fernandez-Aviles et al.[29] | CMI | BMC | Intracoronary | At 6 months among BMC recipients there was decreased ESV, improvement of regional and global LV function, and increased thickness of the infarcted wall. No changes in control group. |
| IACT [30] | CMI | BMC | Intracoronary | At 3 months post BMC administration: decreased myocardial infarct size; improved global and regional LV function; improved maximum oxygen uptake; and improved regional myocardial metabolism relative to non-treated controls. |
| Brehm et al.[31] | CMI | BMC | Intracoronary | Reduced infarct size, increased global LV EF and infarction wall-movement velocity for BMC recipients; no significant changes for control group. Improved maximum oxygen uptake increased regional (18)F-FDG uptake into infarcted tissue. |
| Janssens et al.[32] | CMI | BMC | Intracoronary | Increased mean global LVEF at 4 months in controls and BMC recipients; Decreased myocardial infarct size and better recovery of regional systolic function in BMC group; Increased myocardial perfusion and metabolism in controls and BMC patients. |
| Galinanes et al.[33] | CMI | BMC | Intramyocardial | Unmanipulated BMCs improved global and regional LV function at 6 weeks and 10 months for BMC that received CABG. |
| Fuchs et al.[34, 35] | CMI | BMC | Transendocardial | Among BMC recipients, stable ED LV volume; significant improvementof ESV and EF; improved regional contractility. No significant improvements among controls. |
| Perin et al.[36, 37] | CMI | BMC | Transendocardial | Improved LV EF from baseline and reduction in EDV in treated patients at 4 months. Significant mechanical improvement of injected segments at 4 months. |
| PROTECT-CAD [10, 11] | CMI | BMC | Transendocardial | After 6 months, significant increase in exercise treadmill time and LV F in BMC recipients. Significant decrease in percentage area of peri-infarct regions; increase in global LVEF, percentage of regional wall thickening, and MPR over target area at 6-months. |
| TABMMI [38] | CMI | BMC | Transendocardial | Transmyocardial delivery is safe with trends toward improved cardiac function in a non-randomized pilot trial. |
| vanRamshorst et al.[39] | CMI | BMC | Transendocardial | Significant increase in LV EF for BMC recipients. Filling pressure estimate E/E’ ratio improved at 3 months in BMC group; no improvement in placebo group; significantly larger improvement in E/E(a) ratio for BMC recipients. Significant increase in E/A peak flow ratio in BMC group. |
| Focus-CCTRN [40] | CMI | BMC | Transendocardial | No improvement in cardiac function with autologous BMMC delivered transendocardially. |
| Silva et al.[41] | Heart failure | BMC | Transendocardial | Improved mVO2 and METs for treated patients at 2 and 6 months. No significant difference in ESV, EDV, and LV EF from baseline to 2 or 6 months. |
| Focus-HF [42] | Heart Failure | BMC | Transendocardial | Younger patients had improved cell function with improved responses compared to older patients. |
| TOPCARE-AMI [5, 43–45] | AMI | CPC/BMC | Intracoronary | Persistent improvement of LV EF, significantly decreased LV ESV, and stable LV EDV through 5-year follow up. Significant reduction in functional infarct size. |
| TOPCARE-CHD [46] | CMI | CPC/BMC | Intracoronary | Cross-over study from TOP-CARE AMI. Significantly greater LV EF among BMC vs. CPC recipients and controls. Significant increase in global and regional LV function for BMC recipients, irrespective of cross-over status. |
| Bartunek et al.[47] | AMI | CD133 + BMC | Intracoronary | Significantincrease in LV EF and regional chordae shortening; associated increase in contractilityand decrease in resting MIBI perfusion defect. |
| COMPARE-AMI [48] | AMI | CD133+ BMC | Intracoronary | LVEF improved at 4 months and 1 year compared to placebo treatment. |
| Goussetis et al.[49] | CMI | CD133 + BMC/CD133-CD34 + BMC | Intracoronary | Uptake of cells in the chronic ischemic myocardium. |
| Stamm et al.[50, 51] | AMI | CD133+ BMC | Transendocardial | Enhanced global LV function and improved infarct tissue perfusion in 66% and 83% of BMC recipients, respectively. |
| Stamm et al.[52] | Chronic Ischemic HD | CD133+ BMC | Intramyocardial | Among CABG and cell therapy (vs. CABG alone) recipients, increased LVEF over baseline at discharge, 6, and 18 months and greater improvement in perfusion at the infarction zone. |
| Losordo et al.[53] | CMI | CD34+,G-CSF mobilized PBC | Transendocardial | Improved exercise time at 3 months in placebo and active treatment groups; slightly greater magnitude of improvement in CMI recipients. |
| ACTC34-CMI [54] | CMI/Refractory Angina | CD34+ cells | Transendocardial | Decreased frequency of angina and improved exercise tolerance |
| Choi et al.[55] | AMI | G-CSF mobilized PBC | Intracoronary | Significantly improved LVEF for cell therapy recipients after 6 months. |
| MAGIC Cell-DES [56] | AMI/CMI | G-CSF mobilized PBC | Intracoronary | Significant improvement in LVEF and ESV in cell recipients. In CMI patients, no significant change in LVEF and ventricular remodeling; although, significant improvement of coronary flow reserve. |
| Chachques et al.[57] | MI | Skeletal myoblast | Intramyocardial | serum incubation during cell culture reduces immunological rejection of myoblasts. Significantly improved LV EF and regional wall motion score index in cell-treated segments. |
| Dib et al.[58, 59] | MI | Skeletal myoblast | Intramyocardial | For CABG patients receiving cell transplants there was significant improvement in mean LV EF; increased tissue viability; and reduced ventricular systolic and diastolic volumes. |
| Herreros et al.[60] | MI | Skeletal myoblast | Intramyocardial | In the myoblast group, LVEF, regional contractility (in cardiac segments), global and regional viability and perfusion improved significantly by 12 months. |
| Gavira et. al. [61] | ||||
| Ince et al.[62] | MI | Skeletal myoblast | Transendocardial | Increased LVEF at 12 months and significantly improved walking distance were at 1 year for myoblast recipients. |
| Hagège et al.[63] | Heart failure | Skeletal myoblast | Intramyocardial | Increased LV EF at 1-month and remained stable thereafter (median follow up of 52 months) for myoblast recipients. ACD implantation can reduce arrhythmia risk. |
| Siminiak et al.[64] | AMI | Skeletal myoblast | Intramyocardial | Significantly increased L EF at 4 months; maintained through 12 month follow up. |
| POZNAN [65] | Heart failure | Skeletal myoblast | Transcoronary venous | Increased ejection fraction (3-8%) in two-thirds of cases. |
| Smits et al.[66] | MI/Heart failure | Skeletal myoblast | Transendocardial | Significantly increased LVEF at 3 months, but not at 6 months. At 3 months, significantly increased wall thickening at target areas and less wall thickening in remote areas. |
| MAGIC [67, 68] | CMI | Skeletal myoblast | Intramyocardial | No significant improvement of regional or global LV function for cell groups; significant decrease in LV volumes in high-dose cell group vs. placebo group. |
| Veltman et al.[69] | CMI | Skeletal myoblast | Intramyocardial | No sustained improvement in 14 patients compared to matched controls at 4 year follow-up. |
| Chen et al.[70, 71] | AMI | MSC | Intracoronary | Regional wall movement velocity increased significantly in the MSC group, but not controls. Significantly increased LVEF at 3 months in MSC group compared with baseline and control group. Significantly improved perfusion defect in BMSC group at 3 months compared with control group with synchronous decrease in LV EDV and ESV. Significantly increased ESP: ESV. |
| Chen et al.[72] | CMI | MSC | Intracoronary | For MSC recipients, significant decrease in defect at 12 months; significantly improved level of exercise tolerance and LVEF at 3 months. |
| Hare et al.[73] | AMI | Allogeneic MSC | Intravenous | Increased LVEF in MSC recipients in CMR subset. |
| MSC-HF [74] | Heart Failure | MSC | Transendocardial | Currently enrolling. |
| POSEIDON [75] | CMI | Autologous or Allogeneic MSC | Transendocardial | Allogeneic administration of MSCs is safe and has similar improvements as autologous. |
| TAC-HFT [76, 77] | CMI | MSC or BMC | Transendocardial | Safety of transendocardial delivery of MSCs and BMCs in patients with CMI was found to be safe. |
| MyStromalCell Trial [78] | CMI | ASC | Transendocardial | Currently enrolling using adipose-derived stem cells primed with VEGF-A towards an endothelial progenitor lineage. |
| Frils et al.[79] | Refractory Angina | MSC | Transendocardial | Improved LVEF and systolic wall thickening in CMR subset. |
| Katritsis et al.[80] | AMI | EPC/MSC | Intracoronary | Significantly lower wall motion score index at 4 months in MSC group; Improved myocardial contractility in ≥ 1 previously nonviable myocardial segment and restored uptake of 99mTc in ≥ 1 previously nonviable myocardial scars for BMSC recipients. |
| Lasala et al.[81] | CAD | EPC/MSC | Intracoronary | Significant improvements in LV EF and significant decrease in myocardial ischemia at 1 and 6 months. |