Table 1.
Controlled Clinical Trials of Myocardial Repair with Different Types of Bone Marrow-Derived Cells
| Cell type | Study design | Clinical scenario | Treated patients | Control patients | Route of delivery | Number of cells (millions) | Timing after AMI/PCI | Follow-up duration (months) | Results | |
|---|---|---|---|---|---|---|---|---|---|---|
| A. Cells harvested from the bone marrow | ||||||||||
| ASTAMI (58, 59) | BMMNC | RCT | AMI | 50 | 50 | Intracoronary | 87 ± 47.7 | 6 ± 1.3 days | 12 | No improvement in LVEF, infarct size, and LVEDV |
| Hendrikx et al. (34) | BMMNC | RCT | ICM | 10 | 10 | Intramyocardial (during CABG) | 60 ± 31 | 217 ± 162 days | 4 | Regional wall thickening ⇑; no improvement in global LVEF, LVESV, and LVEDV |
| Karpov et al. (41) | BMMNC | RCT | AMI | 22 | 22 | Intracoronary | 89 ± 49 | 7–21 days | 6 | No improvement in LVEF, perfusion defect, and quality of life |
| Meluzin et al. (63, 64) | BMMNC | RCT | AMI | 40 | 20 | Intracoronary | 10 and 100 | 7 days | 12 | In high cell dose group: global LVEF ⇑; LVESV ⇓; earlier differences in regional wall motion partially lost at 12 month |
| Mocini et al. (67) | BMMNC | Cohort | ICM | 18 | 18 | Intramyocardial (during CABG) | 640 ± 463 | 1–6 months | 12 | In treated patients compared with baseline, global LVEF ⇑; wall motion ⇑ |
| Penicka et al. (76) | BMMNC | RCT | AMI | 17 | 10 | Intracoronary | IQR:1,960-3,300 | 4–11 days | 4 | No improvement in LVEF, infarct size, and LV volumes |
| Perin et al. (77, 78) | BMMNC | Cohort | ICM | 11 | 9 | Transendocardial (EMM-guided) | 25.5 ± 6.3 | NR | 12 | Angina ⇓; NYHA class ⇓; exercise capacity ⇑; perfusion ⇑; no improvement in global LVEF |
| PROTECT-CAD (102) | BMMNC | RCT | CAD with refractory angina | 19 | 9 | Transendocardial (EMM-guided) | 16.7 ± 3.4 (low dose) 42 ± 28 (high dose) |
NR | 6 | Global LVEF ⇑; infarct wall thickening ⇑; LVESV ⇓; exercise time ⇑; NYHA class ⇓ |
| REPAIR-AMI (25, 90, 91) | BMMNC | RCT | AMI | 101 | 103 | Intracoronary | 236 ± 174 | 4.3 ± 1.3 days | 12 | Global LVEF ⇑; regional wall motion ⇑; LVESV ⇓; coronary flow reserve ⇑; no improvement in LVEDV |
| Strauer et al. (97) | BMMNC | Cohort | AMI | 10 | 10 | Intracoronary | 28 ± 22 | 5–9 days | 3 | Stroke volume index ⇑; regional wall motion ⇑; LV contractility index ⇑; infarct size ⇓; LVESV ⇓ |
| Strauer et al. (98) | BMMNC | Cohort | Chronic IHD (prior MI) | 18 | 18 | Intracoronary | 60–132 | 27 ± 31 months | 3 | Global LVEF ⇑; infarct wall motion ⇑; infarct size ⇓; viability ⇑; VO2max ⇑ |
| TCT-STAMI (29) | BMMNC | RCT | AMI | 10 | 10 | Intracoronary | 40 | 1 day | 6 | In treated patients global LVEF ⇑; infarct size ⇓; LV dilation halted |
| TOPCARE-CHD (7) | BMMNC CPC |
RCT | ICM | 35 (BMMNC) 34 (CPC) |
23 | Intracoronary | 205 ± 110 (BMMNC) 22 ± 11 (CPC) |
81 ± 72 months (BMMNC) 77 ± 76 months (CPC) |
6 | Global LVEF ⇑; regional wall motion ⇑ in BMMNC-treated patients |
| BOOST (66, 92, 106) | BMC | RCT | AMI | 30 | 30 | Intracoronary | 2,460 ± 940 | 4.8 ± 1.3 days | 18 | Early differences in global LVEF and regional wall motion between treated and control patients lost significance at 18 months; persistent improvement in diastolic function; no improvement in LVESV, LVEDV, infarct size |
| Janssens et al. (37) | BMC | RCT | AMI | 33 | 34 | Intracoronary | 304 ± 128 | 1 day | 4 | Infarct size ⇓; no improvement in global LVEF, LVESV, and LVEDV |
| Ruan et al. (87) | BMC | RCT | AMI | 9 | 11 | Intracoronary | NR | 1 day | 6 | Global LVEF ⇑; segmental function in the infarct as well as viable area ⇑; LVESV ⇓; LVEDV ⇓ |
| Bartunek et al. (10) | AC133 + BMC | Cohort | AMI | 19 | 16 | Intracoronary | 12.6 ± 2.2 | 11.6 ± 1.4 days | 4 | In treated patients compared with baseline, global LVEF ⇑; regional function ⇑; infarct size ⇓; viability ⇑ |
| Chen et al. (17) | MSC | RCT | AMI | 34 | 35 | Intracoronary | 48,000–60,000 | 18.4 ± 0.5 days | 6 | Global LVEF ⇑; infarct wall motion ⇑; LVESV ⇓; infarct size ⇓; LVEDV ⇓ |
| Chen et al. (16) | MSC | RCT | ICM | 24 | 24 | Intracoronary | 5/ml | 289 ± 168 days | 12 | Perfusion ⇑; NYHA class ⇓; exercise tolerance ⇑ |
| Katritsis et al. (42) | MSC and EPC | Cohort | AMI/ICM | 11 | 11 | Intracoronary | 2–4 | 242 ± 464 days | 4 | Perfusion ⇑; viability ⇑; no improvement in global LVEF, LVESV, and LVEDV |
| B. Mobilized progenitor cells | ||||||||||
| Choi et al. (18) | PBSC | Cohort | AMI | 10 | 63 | Intracoronary | 2,030 ± 690 | 8.3 ± 8.2 days | 24 | Compared with controls, no additional improvement in LV functional or structural parameters |
| Erbs et al. (24, 45) | CPC | RCT | ICM | 13 | 13 | Intracoronary | 69 ± 14 | 7.5 ± 2.9 months | 3 | Global LVEF ⇑; infarct size ⇓; myocardial perfusion ⇑; coronary flow reserve ⇑ |
| Li et al. (55) | PBSC | RCT | AMI | 35 | 35 | Intracoronary | 72.5 ± 73 | 7 ± 5 days | 6 | Global LVEF ⇑; wall motion ⇑; no improvement in LVESV and LVEDV |
| Losordo et al. (57) | CD34 + cells | RCT | CAD with angina | 18 | 6 | Transendocardial (EMM-guided) | 0.05, 0.1, or 0.5 million/kg | NR | 12 | Trend toward improved angina frequency, nitroglycerin usage, CCS class, and exercise time in cell-treated patients |
| MAGIC Cell-3-DES (40) | PBSC | RCT | AMI/ICM | 41 | 41 | Intracoronary | 1400 ± 500 | 7 ± 1 (AMI) 517 ± 525 (OMI) |
6 | In patients with AMI: global LVEF ⇑; LVESV ⇓; infarct size ⇓; coronary flow reserve ⇑. In patients with OMI: coronary flow reserve ⇑ |
| Tatsumi et al. (101) | PBMNC | Cohort | AMI | 18 | 36 | Intracoronary | 4,920 ± 2,820 | 2.5 ± 0.5 days | 6 | Global LVEF ⇑; wall motion ⇑; infarct size ⇓; LVESV index tended to be lower |
| TOPCARE-CHD (7) | BMMNC CPC |
RCT | ICM | 35 (BMMNC) 34 (CPC) |
23 | Intracoronary | 205 ± 110 (BMMNC) 22 ± 11 (CPC) |
81 ± 72 months (BMMNC) 77 ± 76 (CPC) |
6 | No significant improvement in LVEF or wall motion in CPC-treated patients |
AMI, acute myocardial infarction; BMC, unfractionated bone marrow cell; BMMNC, bone marrow mononuclear cell; CAD, coronary artery disease; CCS, Canadian Cardiovascular Society; CPC, circulating progenitor cell; EMM, electromechanical mapping; EPC, endothelial progenitor cell; ICM, ischemic cardiomyopathy; IQR, interquartile range; LV, left ventricular; LVEF, LV ejection fraction; LVEDV, LV end-diastolic volume; LVESV, LV end-systolic volume; MSC, mesenchymal stem cell; NR, not reported; NYHA, New York Heart Association; OMI, old myocardial infarction; PBMNC, peripheral blood-derived mononuclear cell; PBSC, peripheral-derived blood stem cell; PCI, percutaneous coronary intervention; RCT, randomized controlled trial.