Table 2.
Summary of meta-analyses of Bone Marrow Cell Therapy for Ischemic Heart Disease.
| Population | Cells | Studies | No. of Patients | EF HR (95% CI) | Mortality | CHF MACE or CHF Hospitalizations | Ischemic MACE or MI | Other | |
|---|---|---|---|---|---|---|---|---|---|
| Myocardial Infarction | |||||||||
| Hristov et al. (2006) [79] | AMI | BMMC | 5 | 482 | 4.21 (0.21, 8.22) p = 0.04 |
||||
| Abdel-Latif et al. (2007) [26] | IHD | BMMC, BMMesC, CPCs | 18 | 807 | 3.64 (1.56, 5.73) p < 0.001 |
No Δ | ↓LVEDD, ↓ LVESD, ↓ IS | ||
| Lipinski et al. (2007) [82] | AMI | BMMC | 10 | 698 | 3.0 (1.9, 4.1) p < 0.001 |
OR 0.52 (0.16, 1.63) p = 0.26 | OR 0.32 (0.09, 1.21) p = 0.09 |
OR 0.22 (0.05, 0.90) p = 0.04 | Trend ↓LVEDD, ↓ LVESD, ↓ IS |
| Martin-Rendon et al. (2008) [83] | AMI | BMMC | 13 | 811 | 2.99 (1.26, 4.72) p = 0.0007 |
RR 0.62 (0.22, 1.76) p = 0.37 | RR 0.61 (0.12, 2.96) p = 0.54 |
↓ LVESD, ↓ IS | |
| Jeevanantham et al. (2012) [27] | IHD | BMMC, BM-MSCs, | 50 | 2625 | 3.96 (2.90, 5.02) p < 0.00001 |
OR 0.39 (0.27, 0.55) p < 0.00001 | OR 0.52 (0.27, 1.00) p = 0.06 |
OR 0.25 (0.11, 0.57) p = 0.001 | 36 RCT, 14 cohort studies, ↓LVEDD, ↓ LVESD |
| Zimmet et al. (2012) [85] | AMI | BMMCs | 23 | 1317 | 2.70 (1.48, 3.92) p < 0.001 |
OR 0.64 (0.22, 1.72) p = 0.46 | OR 0.62 (0.16, 2.20) p = 0.59 |
RR = 0.66 (0.16, 2.45) p = 0.67 | ↓LVEDD, ↓ LVESD |
| Delewi et al. (2013) [28] | AMI | IC BMMC | 24 | 1624 | 2.23 (1.00, 3.47) p = 0.004 |
RR 0.60 (0.34, 1.08) p = 0.09 | RR 0.59 (0.35, 0.98) p = 0.04 |
RR 0.44 (0.24, 0.79) p = 0.007 | No Δ in LVEDD or LVESD |
| de Jong et al. (2014) [29] | AMI | BMMC, BM-MSCs | 2.10 (0.68, 3.52) p = 0.004 |
OR 0.68 (0.36, 1.31) p = 0.25 | OR 0.14 (0.03, 0.52) p = 0.003 |
OR 0.5 (0.24, 1.06) p = 0.07 | ↓ LVESD, ↓ IS | ||
| Xu et al. (2014) [84] | IHD | BMMC, CPCs | 19 | 886 | 3.54 (1.92, 5.17) p < 0.001 |
RR 0.49 (0.28, 0.84) p = 0.01 | RR 0.29 (0.06, 1.53) p = 0.14 | No Δ LVEDD, ↓ LVESD | |
| Fisher at al. (2016) [76] | AMI | BMMC, BM-MSC, CD34+ or CD133+ cells | 41 | 2739 | 0.27 (-1.13, 1.67) p = 0.70 | HR 0.92 (0.62, 1.36) p = 0.67 | HR 0.36 (0.21, 0.61) p = 0.002 |
HR 0.63 (0.40, 1.01) p = 0.05 | |
| Gyongyosi et al. (2015) [78] | AMI | IC BMMC | 12 | 767:485 | 1.15 (-0.38, 2.69) p = 0.14 |
HR 0.81 (0.57, 1.16) p = 0.25 |
HR 0.52 (0.28, 1.08) p = 0.08 | No Δ in LVEDD or LVESV, patient level analysis | |
| Ischemic Cardiomyopathy | |||||||||
| Kandala et al. (2013) [80] | HFrEF (ICM) | BMMC | 10 | 519 | 4.48 (2.43, 6.53) p < 0.0001 |
↓LVEDD, ↓ LVESD |
|||
| Fisher et al. (2015) [77] | HFrEF (ICM) | BMMC, CPCs, | 31 | 1521 | 2.06 (1.1, 3.01) p < 0.0001 |
RR 0.48 (0.34, 0.69) p < 0.0001 |
RR 0.39 (0.22, 0.70) p = 0.002 |
Multiple different study types, cells, delivery mechanisms, and additional procedures (PCI/CABG) at time of cell delivery | |
| Refractory Angina | |||||||||
| Fisher et al. (2013) [30] | CIHD | BMMC and CD34+ Cells | 9 | 659 | RR 0.33 (0.17, 0.65) p = 0.001 |
↓CCS angina class, ↓ AF | |||
| Li et al. (2013) [81] | CIHD | BMMC and CD34+ Cells | 5 | 381 | OR 0.33 (0.08, 1.39) p = 0.13 |
OR 0.37 (0.14, 0.95) p = 0.04 | ↑ETT (61.3 s [18.1, 104.4] p = 0.005; ↓ AF | ||
| Henry et al. (2018) [69] | CIHD | CD34+ Cells | 3 | 304 | K-M rate 2.5% (CD34+) vs. 12.1% (placebo) p = 0.0025 |
30.0% (CD34+) vs. 38.9% (Placebo) p = 0.14 |
↑ETT (49.5 s [9.3, 89.7] p = 0.016; RR AF 0.66 (p = 0.012) |
||
AF indicates angina frequency; AMI, acute myocardial infarction; BMMC, bone marrow mononuclear cells; BMMesC, bone marrow derived stem cells; BM-MSC, bone marrow mesenchymal cells; CABG, coronary artery bypass graft; CCS, Canadian Cardiovascular Society; CHF, congestive heart failure; CIHD, chronic ischemic heart disease; CPC, cardiac progenitor cells; EF, ejection fraction; ETT, exercise tolerance test; HFrEF, heart failure with reduced ejection fraction; IC, intracoronary; IHD, ischemic heart disease; ICM, ischemic cardiomyopathy; IS, infarct size; K-M, Kaplan-Meier; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; MACE, major adverse cardiovascular events; MI, myocardial infarction; PCI, percutaneous coronary intervention; RCT, randomized controlled trial; RR, Relative Risk.