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©The Author(s) 2024.
World J Cardiol. Aug 26, 2024; 16(8): 469-483
Published online Aug 26, 2024. doi: 10.4330/wjc.v16.i8.469
Published online Aug 26, 2024. doi: 10.4330/wjc.v16.i8.469
Table 1 Baseline characteristics of randomized clinical trials included in the meta-analysis for mortality in umbilical-cord-derived mesenchymal-stem-cell-based heart therapy, n (%)
| Gao et al[21], 2015 (China) | He et al[18], 2020 (China) | Zhao et al[26], 2015 (China) | Bartolucci et al[28], 2017 (Chile) | Ulus et al[25], 2020 (Türkiye) | ||
| Study type | RCT | RCT | RCT | RCT | Open-label RCT | |
| Phase | I/II | I | I/II | I/II | I/II | |
| Sample size | Total | 116 | 50 | 59 | 30 | 41 |
| Intervention (male) | 58 (94.8) | 32 (78.12) | 30 (80.0) | 15 (80.0) | 25 (100) | |
| Control (male) | 58 (87.9) | 12 (58.30) | 29 (65.5) | 15 (93.3) | 16 (100) | |
| Mean age (mean ± SD) | Intervention | 57.3 ± 9.90 | 59.6 (7.9)/63.6 (8.6) | 52.90 ± 16.32 | 57.33 ± 10.05 | 61.8 ± 10 |
| Control | 56.7 ± 12.95 | 65.2 (7.9) | 53.21 ± 11.46 | 57.20 ± 11.64 | 65.3 ± 6.8 | |
| Mean BMI (mean ± SD) | Intervention | 24.9 ± 2.28 | 25.5 ± 3.3 /24.4 ± 3.3 | N/A | 29.12 ± 2.88 | 26.5 ± 4.5 |
| Control | 25.4 ± 2.28 | 23.59 ± 2.28 | N/A | 29.52 ± 4.00 | 26.6 ± 4.8 | |
| Number of smokers | Intervention | 34 (58.6) | 4 (25.0)/7 (43.8) | N/A | 7 (46.7) | 21 (84) |
| Control | 32 (55.2) | 3 (25.0) | N/A | 4 (26.7) | 15 (88.2) | |
| HTN | Intervention | 33 (56.9) | 10 (62.5)/14 (87.5) | N/A | 7 (46.7) | 15 (60) |
| Control | 26 (44.8) | 9 (75.0) | N/A | 8 (53.3) | 11 (64.7) | |
| DM | Intervention | 17 (29.3) | 8 (50.0)/4 (25.0) | N/A | 5 (33.3) | 16 (66.7) |
| Control | 14 (24.1) | 8 (66.7) | N/A | 7 (46.7) | 9 (52.9) | |
| NYHA; I (n), II (n), III (n), IV (n) | Intervention | N/A | III (4 / 8), IV (12 / 8) | N/A | 2.03 ± 0.61 | 1.9 ± 0.44 |
| Control | N/A | III (7) IV (5) | N/A | 1.67 ± 0.49 | 2.1 ± 0.37 | |
| Comparison | Placebo | CABG only | HF drugs only | Placebo | CABG only | |
| Follow-up, months | 1, 4, 12 and 18 mo | 3, 6 and 12 mo | 1 and 6 mo | 3, 3, 6 and 12 mo | 1, 3, 6 and 12 mo | |
| Assessment modality (yes/no) | ECG | Yes | - | Yes | Yes | Yes |
| Echo | Yes | - | Yes | Yes | Yes | |
| MRI | No | Yes - CMR | - | Yes - CMR | Yes | |
| Cardiac CT | Yes | - | - | - | No | |
| SPECT | Yes | - | - | - | Yes | |
| Measured outcomes | Safety and adverse event (primary), efficacy, and LV functions LVEF (secondary) | Serious adverse events at 12 mo (primary), the efficacy of hUC-MSCs and collagen scaffold assessed according to the CV-CMR-based LVEF and infarct size at 3, 6 and 12 mo after treatment, and NYHA (secondary) | Changes in LVEDD, LVEF, BNP, 6MWD, symptoms of HF, death, and adverse events | Safety: Adverse events after IV infusion -/-. Efficacy: (primary). Change in LVEF in ECHO, changes in - (LVESV) & (LVEDV) at ECHO; LVEF, LVESV, and LVEDV in CMR; NYHA score (secondary) | LVEF, LV remodeling, myocardial mass, 6MWD, NYHA score change | |
Table 2 Baseline characteristics of randomized clinical trials included in the meta-analysis of bone-marrow-derived mesenchymal-stem-cell-based cardiac therapy, n (%)
| Chullikana et al[29], 2015 (India) | Hare et al[30], 2009 (USA) | Heldman et al[34], 2014 (USA) | Mathiasen et al[31], 2015 (Denmark) | Xiao et al[27], 2017 (China) | ||
| Study type | RCT | RCT | Open label RCT | RCT | Open label RCT | |
| Phase | I/II | I | I/II | I/II | I/II | |
| Condition | MI | MI | HF | HF | HF | |
| Sample size | Total | 20 | 53 | 30 | 60 | 37 |
| Intervention (male) | 10 (100) | 34 (82.4) | 19 (94.7) | 40 (90) | 17 (70) | |
| Control (male) | 10 (80) | 19 (78.9) | 11 (90.9) | 20 (70) | 20 (70) | |
| Mean age (mean ± SD) | Intervention | 47.31 ± 12.10 | 59 ± 12.3 | 57.1 ± 10.6 | 66.1 ± 7.7 | 51.6 ± 12.2 |
| Control | 47.79 ± 6.48 | 55 ± 10.2 | 60.0 ± 12.0 | 64.2 ± 10.6 | 54.4 ± 11.6 | |
| Mean BMI (mean ± SD) | Intervention | 23.32 ± 3.74 | 29.8 ± 6.7 | N/A | 29.8 + 4.7 | N/A |
| Control | 24.86 ± 1.88 | 30.3 ± 4.3 | N/A | 28.7 ± 5.3 | N/A | |
| Number of smokers | Intervention | N/A | 3 (8.8) | 14 (73) | 7 (17) | N/A |
| Control | N/A | 2 (10.5) | 9 (81.9) | 1 (5) | N/A | |
| HTN | Intervention | N/A | 16 (17.6) | 12 (63.2) | 0 | 4 (23) |
| Control | N/A | 9 (47.4) | 6 (54.5) | 0 | 7 (35) | |
| DM | Intervention | N/A | 6 (17.6) | 3 (15.8) | 15 (37) | 5 (29.4) |
| Control | N/A | 1 (5.3) | 3 (27.3) | 3 (15) | 6 (30) | |
| NYHA; I (n), II (n), III (n), IV (n) | Intervention | N/A | N/A | I (5)/II (12)/III (2) | II (11)/III (29) | II |
| Control | N/A | N/A | I (2)/II (5)/III (3) | II (5)/III (15) | II | |
| Comparison | Placebo (multiple electrolytes injection) | Placebo | HF treatments | HF treatments | HF treatments | |
| Follow-up | 6 mo to 2 yr | 6 mo | 12 mo | 6 mo | 12 mo | |
| Assessment modality (yes/no) | ECG | No | Yes | Yes | No | Yes |
| Echo | Yes | Yes | No | No | Yes | |
| MRI | Yes | Yes | Yes | Yes | No | |
| Cardiac CT | No | Yes | Yes | Yes | No | |
| SPECT | Yes | No | No | No | Yes | |
| Measured outcomes | Adverse events, LVEF (Echo and SPECT), total perfusion score, and total infarct volume | Safety, adverse events, LVEF (Echo), and 6MWD | Adverse events (primary), 6MWD, NYHA, and LV parameters (secondary) | LVESV (primary), LVEF, NYHA, 6MWD, and LV parameters (secondary) | LVEF, NYHA, LVEDV, and MAE are primary endpoints | |
Table 3 Baseline characteristics of randomized clinical trials included in the meta-analysis of bone-marrow-derived mesenchymal-stem-cell-based cardiac therapy, n (%)
| Ulus et al[25], 2020 (Türkiye) | Rodrigo et al[32], 2013 (Netherlands) | Kim et al[16], 2018 (South Korea) | Bolli et al[23], 2020 (USA) | ||
| Study type | Open-label RCT | RCT | RCT | RCT | |
| Phase | I/II | I/II | I | I | |
| Condition | CIC | MI | MI | HF | |
| Sample size | Total | 28 | 54 | 26 | 31 |
| Intervention (male) | 12 (100) | 9 (78) | 14 (100) | 14 (43) | |
| Control (male) | 16 (100) | 45 (78) | 12 (100) | 17 (24) | |
| Mean age (mean ± SD) | Intervention | 56.9 ± 5.20 | 56 ± 8 | 55.3 ± 8.6 | 54.7 ± 12.8 |
| Control | 65.3 ± 6.8 | 61 ± 11 | 57.8 ± 8.9 | 58.2 ± 11.2 | |
| Mean BMI (mean ± SD) | Intervention | 26.2 ± 3.12 | N/A | N/A | 30.2 ± 9.0 |
| Control | 26.6 ± 4.8 | N/A | N/A | 30.4 ± 6.5 | |
| Number of smokers | Intervention | 11 (91.6) | 6 (67) | 5 (35.7) | 5 (36) |
| Control | 15 (88.2) | 19 (42) | 5 (41.7) | 3 (18) | |
| HTN | Intervention | 6 (50) | 4 (44) | 5 (35.7) | 6 (43) |
| Control | 11 (64.7) | 18 (40) | 5 (41.7) | 10 (59) | |
| DM | Intervention | 4 (33.3) | 1 (11) | 3 (21.4) | 3 (21) |
| Control | 9 (52.9) | 5 (11) | 2 (16.7) | 5 (29) | |
| NYHA; I (n), II (n), III (n), IV (n) | Intervention | 2.2 ± 0.6 | N/A | N/A | II (13), III (1) |
| Control | 2.1 ± 0.37 | N/A | N/A | II (13), III (4) | |
| Comparison | CABG only | No placebo (optimal MI treatment) | No placebo (optimal MI treatment) | HF treatments | |
| Follow-up duration | 1, 3, 6, and 12 mo | 3, 6, 12 mo, 4, 5 years | 4 and 12 mo | 6 and 12 mo | |
| Assessment modality (Yes/no) | ECG | Yes | Yes - Holter | No | Yes |
| Echo | Yes | Yes | Yes | No | |
| MRI | Yes | No | No | Yes - CMR | |
| Cardiac CT | No | No | No | No | |
| SPECT | Yes | Yes | Yes | No | |
| Measured outcomes | LVEF, LV remodeling, myocardial mass, 6MWD, NYHA score | Safety and feasibility of IM delivery after PCI for MI (primary). Efficacy regarding change in infarct size, LVEF, LVEDV, and LVESV (secondary) | Absolute changes in global LVEF from baseline to 4 months after PCI using SPECT, Echo changes in global LVEF at 12 mo (primary). Changes in LVEDV, LVESV, and MACE (secondary) | Safety and feasibility of allogenic MSC in population (primary). Effects of allogenic MSC on LV function (LVEF, LVEDV, LVESV, scar), morphology, and functional status (6MWD, MLHFQ) (secondary) | |
Table 4 Intervention characteristics of randomized controlled trials of umbilical-cord-derived mesenchymal stem cells
| Refs | Cell type | Cell condition | MSCs dose and volume | Route of delivery | Concurrent procedure (if any) |
| He et al[18] | WJUC-MSCs | Frozen | 1 × 108/1.5-2.5 mL +/- 1 mL collagen scaffold | IM | CABG for all groups |
| Zhao et al[26] | UC-MSCs | N/S | N/S | IC | N/A |
| Bartolucci et al[28] | WJUC-MSCs | Frozen | 1 × 106/kg in 100 mL | IV | N/A |
| Ulus et al[25] | UC-MSCs | Frozen | 23 × 106 | IM | CABG for all groups |
| Gao et al[21] | WJUC- MSCs | Fresh | 6 × 106 | IC | N/A |
Table 5 Intervention characteristics of randomized controlled trials of bone-marrow-derived mesenchymal stem cells
| Refs | Cell type | Cell condition | Cell source | MSCs dose and volume | Route of delivery | Concurrent procedure (if any) |
| Chullikana et al[29] | BM-MSCs | Frozen | Allogenic | 2 million cells/kg, 0.5 mL/kg | IV | N/A |
| Hare et al[30] | BM-MSCs | Frozen | Allogenic | 0.5, 1.6, and 5.0 × 106 | IV | N/A |
| Heldman et al [34] | BM-MSCs | Fresh | Autologous | N/A | IC | PCI |
| Mathiasen et al[31] | BM-MSCs | Fresh | Autologous | 77.5 ± 67.9 × 106 in 10-15 injections | IM | N/A |
| Xiao et al[27] | BM-MSCs | Fresh | Autologous | 4.9 × 108 | IC | N/A |
| Ulus et al[25] | BM-MSCs | Fresh | Autologous | 70 × 107 | IM | CABG |
| Rodrigo et al[32] | BM-MSCs | Fresh | Autologous | 31 ± 2 × 106 IN 10-12 injections | IM | N/A |
| Kim et al[16] | BM-MSCs | Fresh | Autologous | 7.2 ± 0.90 × 107 | IC | N/A |
| Bolli et al[23] | BM-MSCs | Frozen | Allogenic | 1 × 108 via 20 TC injections | IM | N/A |
- Citation: Safwan M, Bourgleh MS, Aldoush M, Haider KH. Tissue-source effect on mesenchymal stem cells as living biodrugs for heart failure: Systematic review and meta-analysis. World J Cardiol 2024; 16(8): 469-483
- URL: https://www.wjgnet.com/1949-8462/full/v16/i8/469.htm
- DOI: https://dx.doi.org/10.4330/wjc.v16.i8.469