Table 1.
List of cell therapy clinical trials in cardiac diseases according to the type of cells used
| Cell types | Studies | Auto Allo | Random | Diseases | Average Cell doses | Route | Number of patients | Results | F.U. |
|---|---|---|---|---|---|---|---|---|---|
| Myoblasts | |||||||||
| MAGIC Menasché et al. [8] | Auto |
Yes:3 groups C; LD; HD |
MI |
LD: 4 .108 HD: 8.108 |
IM |
Subjects: 97 Controls: 30 |
Neutral | 6 months | |
| BM-MNCs | |||||||||
|
Meta-Analysis Martin-Rendon et al. [9] |
Auto |
Yes: 2 groups C; MNCs |
AMI |
1.107 to 2,5.109 |
IC |
Subjects: 326 Controls: 312 |
LVEF: ↗ LVESV: ↗ |
6 to 12 months | |
|
Meta-Analysis Brunskill et al. [10] |
Auto |
Yes: 2 groups C; MNCs |
AMI/CHF | 107 to 108 |
IC:20 trials IM: 5 trials |
Subjects: 565 Controls: 526 |
IC - LVEF: 0 IM - LVEF: ↗ AMI > IHD |
6 months | |
|
Am Heart J 2006 Meluzin et al. [11] |
Auto |
Yes: 3 groups C; LD; HD |
AMI |
LD: 107 HD: 108 |
IC | 66 (22 in each group) |
LVEF ↗ in HD LVESV↘ in HD |
3 months | |
|
Meta-Analysis Jeevanantham et al. [12] |
Auto |
Yes: 35 trials No: 15 trials |
AMI/CHF | 106 to 109 |
Trials Nb: IC:38 IM:12 |
Subjects:1460 Controls1165 |
LV function ↗ Remodelling ↗ |
4 to 36 months |
|
|
Meta-Analysis Delewi et al. [13] |
Auto |
Yes:2 groups C; MNCs |
AMI | 50–400.106 | IC |
Subjects: 984 Controls: 657 |
LV function ↗ in younger and severe patients | 3 to 6 months | |
|
ACCRUE Meta-Analysis Gyöngyösi et al. [89] |
Auto |
Yes (Prospective) C; MNCs |
AMI | 150 .106 | IC |
Subjects: 767 Controls: 485 |
Neutral |
3 to 12 months |
|
|
REPAIR-AMI trial Schächinger et al. [93] |
Auto |
Yes: 2 groups C; MNCs |
AMI | 198.106 | IC |
Subjects: 101 Controls: 103 |
LVEF↗ only in more severe patients | 12 months | |
|
BOOST trial Meyer et al. [95] |
Auto |
Yes: 2 groups C; MNCs |
AMI | 24,6 ± 9,4.106 | IC |
Subjects: 30 Controls: 30 |
Neutral | 18 months | |
| 34+SCs | |||||||||
|
POC Study Pasquet et al. [25] |
Auto (PB) |
No | AMI | 52.106 | IM | Subjects: 7 |
LVEF ↗↗↗ Cardiac repair |
24 months | |
|
Amer Heart J 2011 Quyyumi et al. [24] |
Auto (BM) |
Yes: 4groups LD; MD; HD C |
AMI | 5;10;15.106 | IC |
Subjects: 16 Controls: 15 |
LVEF ↗↗ if 34+ SCs ≥ 107 |
6 months | |
|
REGENT Tendera et al. [36] |
Auto (BM) |
Yes: 2 groups MNC, 34+SC |
AMI | MNC:1,8.108 34+:1,9.106 | IC |
MNCs: 80 34+ SCs: 80 |
Neutral | 6 months | |
|
PRESERVE – AMI Quyyumi et al. [37] |
Auto (BM) |
Yes C; 34+SC |
AMI | 8–44.106 | IC |
Subjects: 78 Controls: 83 |
LVEF ↗↗ if 34+SCs ≥20 × 106 |
12 months | |
|
Circ Res 2013 Vrtovec et al. [38] |
Auto (PB) |
Yes C; 34+SC |
CHF | 113 ± 26.106 | IC |
Subjects: 55 Controls: 55 |
LV function↗ TET ↗ |
60 months | |
|
Circ Res 2011 Losordo et al. [39] |
Auto (PB) |
Yes:3 groups C; LD; HD |
RA |
LD: 1.105/kg HD:5.105/kg |
IM |
Subjects: 111 LD: 55 HD: 56 Controls: 56 |
Less angina crisis (LD) TET ↗ (LD) |
12 months | |
|
RENEW trial Povsic et al. [40] |
Auto (PB) |
Yes:3 groups SOC; C; 34+SC |
RA | 1.105/kg | IM |
Subjects: 50 SOC: 6 Controls: 28 |
Less angina TET ↗ Less MACE |
Early closure | |
| MSCs | |||||||||
|
Meta-analysis Jeong et al. [51] |
Auto [9] Allo [5] |
Yes: 2 groups C, MSCs |
AMI: 6 IHF: 6 |
Auto:1–25.106 Allo: 2–72.106 |
IM:4 trials IC: 5 trials IV: 3 trials |
Subjects: 509 Controls: 441 |
LVEF ↗ Mass scar: - 1.13 |
24 months | |
|
JACC 2009 Hare et al. [52] |
Allo (BM) |
Yes: 4 groups C; LD; MD; HD |
AMI |
LD: 0,5.106/kg MD:1,6,106/kg HD: 5.106/kg |
IV |
Subjects: 39 Controls: 21 |
LVEF ↗ | 6 months | |
|
POSEIDON trial Hare et al. [53] |
Auto vs Allo (BM) |
Yes dose ranging: 6 sub-groups |
IHF |
LD: 20.106 MD: 100.106 HD: 200.106 |
IM |
Auto: 15 Allo: 15 |
Trends towards infarct size reduction and reverse remodeling | 12 months | |
|
Cytotherapy 2015 Chullikana et al [54] |
Allo (BM) |
Yes C, MSCs |
AMI | 2.106/kg | IV |
Subjects: 10 Controls: 10 |
Neutral | 24 months | |
|
Circ Res 2015 Perin et al. [55] |
Allo (BM) |
Yes: 4 groups LD; MD;HD C |
IHF NIHF |
LD: 25.106 MD: 75.106 HD: 150.106 |
IM |
Subjects: 45 Controls: 15 |
LVESV LVEDV ↘ with HD |
36 months | |
|
TRIDENT Study Florea et al. [56] |
Allo (BM) |
Yes: 2 groups LD, HD |
MI |
LD: 20.106 HD: 100.106 |
IM |
LD: 15 HD: 15 |
Scar size reduction LVEF ↗ in HD |
12 months | |
|
Am J Cardiol 2004 Chen et al. [57] |
Auto (BM) |
Yes: 2 groups C, MSCs |
AMI | 8–10.109 | IC |
Subjects: 35 Contols: 34 |
Wall movement ↗ LVEF ↗ |
24 months | |
|
Inter J Cardiol 2013 Gao et al. [59] |
Auto (BM) |
Yes: 2 groups C, MSCs |
AMI | 3,08 ± 0,52.106 | IC |
Subjects: 21 Controls: 22 |
Neutral | 12 months | |
|
MSC--HF trial Mathiasen et al. [60] |
Auto (BM) |
Yes: 2 groups C, MSCs |
MI | 77.5 ± 67.9.106 | IM |
Subjects: 40 Controls: 20 |
LVESV ↘ LVEF ↗ |
6 months | |
| CDCs | |||||||||
|
CADUCEUS trial Makkar et al. [69] |
Auto (Cardiac Biopsy) |
Yes: 2 groups C; CDCs |
MI | 12,5–25.106 | IC |
Subjects: 17 SOC: 8 |
Scar mass ↘ Wall thickening |
6 months | |
| CPCs | |||||||||
|
C - CURE trial Bartunek et al. [71] |
Auto (BM) |
Yes: 2 groups SOC, CPCs |
ICHF | ≥ 600 .106 | IM |
Subjects: 32 Controls: 15 |
LVEF ↗ TET ↗ LVESV ↘ |
6 months | |
| CHART-1 trial |
Auto (BM) |
Yes: 2 groups Sham, CPCs |
ICHF | ≥ 600 .106 | IM | ||||
|
1-Bartunek et al. [73] 2- Teerlink et al. [74] |
Subjects: 120 Sham: 151 Subjects: 157 Sham: 158 |
Neutral primary endpoint LVESV↘ LVEDV↘ |
39 weeks 52 weeks |
||||||
Abbreviations: Auto/Allo, autologous/allogeneic; F.U., follow-up; BM, bone marrow; PB, peripheral blood; BM-MNCs, bone marrow mononuclear cells; 34+ SC, CD34+ stem cells; MSCs, mesenchymal stem cells; CDCs, cardiosphere-derived cells; CPCs, cardiopoietic cells; C, controls; LD/ MD/HD, low/mid/high doses; MI, myocardial infarct; AMI, acute myocardial infarct; CHF, chronic heart failure; RA, refractory angina; IHF, ischemic heart failure; NIHF, non-ischemic heart failure; IM/IC/ IV, intra-myocardial/intra-coronary, intra-venous cell delivery; LV, left ventricle; LVEF, left ventricle ejection fraction; LVESV, left ventricle end systolic volume; LVEDV, left ventricle end diastolic volume; TET, total exercise time; MACE, major adverse cardiovascular events; SOC, standard of care; POC, proof of oconcept. ↗/↗↗/↗↗↗, weak/ significant/ highly significant increase. ↘, weak decrease