Skip to main content

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, 1921] 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, 4345] 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.
  1. Abbreviations: AMI acute myocardial infarction, BMC bone marrow cell, E peak early transmitral velocity, A peak late transmitral velocity, E(a) early diastolic velocity, A(a) late diastolic velocity, DT E-wave deceleration time, IVRT isovolumic relaxation time, BM bone marrow, LV left ventricular, ESV end-systolic volume, EF ejection fraction, EDV end-diastolic volume, CAD coronary arterial disease, CMI chronic myocardial infarction, F fluorine, FDG fluordeoxyglucose, MI myocardial infarction, BMMC mononuclear bone marrow cell, STEMI ST-elevation myocardial infarction, mVO2 myocardial volume oxygen consumption, MPR myocardial perfusion reserve, METs metabolic equivalents, CPC circulating blood derived progenitor cells, HD heart disease, CD133+/CD34+ bone marrow-derived CD133+ or CD34+ cells, G-CSF granulocyte colony stimulating factor, PBC peripheral blood cell, MI myocardial infarction, CABG coronary artery bypass graft surgery, MSC bone marrow-derived mesenchymal stem cells, ASC adipose-derived stem cells, ESP end-systolic pressure, Tc Technetium.