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. 2021 Aug 9;13(8):e17022. doi: 10.7759/cureus.17022

Table 2. Characteristics and outcomes of the included studies.

STEMI = ST-Elevation Myocardial Infarction, CAG = Coronary Angiography, PCI = Percutaneous Coronary Intervention, PPCI = Primary Percutaneous Coronary Intervention, LVEF = Left Ventricular Ejection Fraction, CABG = Coronary artery bypass grafting, CK = Creatine Kinase, H/o = History of, MI = Myocardial Infarction, CCT = Controlled Clinical Trial, CT = Clinical Trial, MNC = Mononuclear stem cells, CCTA = Coronary Computed Tomography Angiography, RCT = Randomized Controlled Trial, BMMNC = Bone Marrow Mononuclear Cell, BNP = B-type natriuretic peptide, WMSI = Wall Motion Score Index, N-BMC = Normoxia Bone Marrow Mononuclear Cells, HP-BMC = Hypoxia Preconditioned Bone Marrow Mononuclear Cells, ECG = Electrocardiogram, SPECT = Single-Photon Emission Computed Tomography, LV = Left Ventricle, MRI = Magnetic Resonance Imaging, CT scan = Computed Tomography scan, F-18-FDG-PET = F-18-Fluorodeoxyglucose Positron Emission Computed Tomography, 99mTc-SPECT= 99mTc-sestamibi Single-Photon Emission Computed Tomography, G-CSF = Granulocyte Colony-Stimulating Factor, MSCs = Mesenchymal Stem Cells, WJ-MSC = Wharton’s jelly-derived Mesenchymal Stem Cells, CDC = Cardio sphere-derived autologous stem cell, LVEDD = End-Diastolic Dimension of the Left Ventricle, LVESV = End-Systolic Volume of the Left Ventricle, LVEDV = End-Diastolic Volume of the Left Ventricle, SPCs = Stem/ Progenitor Cells, LIN- = Lineage-negative, CADUCEUS = CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction, TIME trial = Timing in Myocardial Infarction Evaluation trial

Author Country/Year Study design Patient characteristics Sample size Treatment group Control group Follow-up period Outcome
Benedek et al. [8] Romania / 2014 CCT Adult with h/o STEMI and PPCI and abnormalities in wall motion and less than 50% stenosis 18 Autologous MNC = 9   Placebo = 9   Four years with clinical examinations, ECG, Echocardiography, 64-slice CCTA A small improvement in EF and the plaque burden is lower in coronary segments treated with stem cells    
Alestalo et al. [9] Finland / 2015     Double-blinded RCT H/o STEMI, < 75 years, hemodynamically stable and no cardiogenic shock or rescue PCI/CABG     26 BMMNC = 14     Placebo = 12   Cytokines after four days and LV angiogram after six months A balancing effect between the anti-inflammatory and proinflammatory cytokine BMMNC group at day four
Bozdag-Turan et al. [10]  Germany / 2012   CCT   18–80 years with h/o STEMI, absence of co-morbidities, cancer, and active bleeding or trauma in the last two months  24 BMC = 12 Placebo = 12 Six months with left ventriculography Infarct size and BNP level decreased, and global EF and infarct wall movement velocity were increased in the stem cell group  
Choudry et al.  [11] 5 centers in Europe [United Kingdom (3); Switzerland (1); Denmark (1)] / 2016 Double-blinded RCT   Acute anterior MI with anterior wall motion abnormality and h/o PPCI   100 BMMNC = 55   Placebo = 45   One year with cardiac MRI and Echocardiography Small non-significant improvement in LVEF  
Duan et al. [12] China / 2015   RCT   H/o MI, < 75 years with planned CABG for triple-vessel disease, LVEF < 30%, and no aneurysm or valvular diseases 42 CABG + BMMNC = 24 Only CABG  = 18 One year with Echocardiography Improvement in left ventricular functions in the treatment group    
Gao et al. [6] China / 2015   Double-blinded RCT   18-80 years with a h/o STEMI and reperfusion with stent implantation and LV local wall-motion abnormality. CK > three-fold the upper limit of the normal  116 WJ-MSC = 58   Placebo = 58 18 months with F-18-FDG-PET and 99mTc-SPECT and two-dimensional Echocardiography   LVEF significantly increased and LVESV and LVEDV greatly decreased in the treatment group 
Hu et al. [13] China / 2015 RCT   18-75 years old with acute STEMI and PPCI with stent implantation or thrombolysis and LV local wall motion abnormality   36 N-BMCs = 11, HP-BMCs = 11   Standard therapy = 14 Six and 12 months Improvement in changes of LVEDV, LVESV, and WMSI in the HP-BMC group. Myocardial perfusion defect ratio was reduced in HP-BMCs and N-BMC groups at six months  
Huan et al. [14] China / 2015 CT   18-75 years old with a h/o acute STEMI and treatment with PCI, LVEF < 50% 104 Group A = BMMNC within two hours after PCI = 27, Group B = three-seven days after PCI = 26, Group C = seven to 30 days after PCI = 26 Placebo = 25 patients Six months with angiography. SPECT and Echocardiography at six and 12 months Effects of cell therapy given within 24 hours are the same as to given three-seven days after PPCI
Kim et al. [15] South Korea / 2018   RCT   STEMI 26 BMMNC = 14 Placebo = 12 Four and 12-months with SPECT   Increase in the LVEF from baseline to the fourth month and twelfth month in the bone marrow mesenchymal stem cells group.  
Lee et al.  [16] Korea / 2014   CT   18-70 years old with STEMI 69 MSC = 33   Placebo = 36 Six months with SPECT Safe with modest improvement in LVEF
Makkar et al. [17] USA / 2012   CT   H/o two to four weeks of MI and LVEF = 25–45%   25 Cardio sphere-derived autologous stem cells = 17   Standard therapy = 8 Six months with MRI Scar mass was reduced, increase in viable heart mass and regional contractility in the CDC group.   LVEDV, LVESV, and LVEF were the same in the two groups  
Malliaras et al.  [18] USA / 2014 RCT   Patients of CADUCEUS trial were followed up for a year 25 Cardio sphere-derived autologous stem cells = 17   Standard therapy = 8 One year with MRI Scar size reduced, increased viable myocardium, and improved regional function of infarcted myocardium 
Micheu et al. [19] Romania / 2015   CT 18-81 years old with STEMI & h/o angioplasty with stent implantation, LVEF < 40%.   18 Autologous BMCs = 7 Standard therapy = 11 Six months with clinical examination, Echocardiography, 24 hours ECG Safe and LVEF was increased 
Moccetti et al. [20] Switzerland / 2012  CT   Acute anterior STEMI treated by PPCI and LVEF < 50%.    60 Autologous BMMNC = 23   Standard therapy = 37 Five years with Echocardiography Safe and LV function improved    
Moreira et al.  [21] Brazil / 2011 RCT   18-80 years old with h/o MI and reperfusion and involving more than 10% of the LV   30 BMMNC via anterograde intra-arterial coronary (IAC) delivery = 14, BMMNC via retrograde intravenous coronary (IVC) delivery = 10   Placebo = 6   Cardiac MRI was performed before cell injection   The retrograde approach to deliver stem cells was safe and cell retention by cardiac tissue is more in the anterograde approach  
Nair et al.  [22] India / 2015 RCT   Anterior MI and LVEF = 20-50%, 20-65 years with h/o CAG between one to three weeks   250 Stem cell therapy + standard care = 125 Standard care = 125 Six months with Echocardiography Safe, but not clinically significant
Naseri et al.  [23] Iran / 2018 RCT 18-75 years old with a h/o acute MI infarction, eligible for elective CABG 77 CD133 (+) = 21, MNC = 30 Placebo = 26 Six and 18 months after CABG with SPECT Significant differences were seen between the MNC and placebo groups in LVEF and a decrease in the LV thickening  
Nicolau et al.  [24] Brazil / 2018 RCT 30-80 years, LVEF ≤ 50%, and regional dysfunction in the infarct-related area  120 BMMNC = 66 Placebo = 55 Six months with MRI No significant effects
Peregud-Pogorzelska et al. [25] Poland / 2020 CCT not randomized    <65 years old with first MI and EF ≤ 45%   34 Standard therapy + autologous BM-derived LIN- SPCs = 15 Only standard therapy = 19 One, three, six months, and one year with Echocardiography Safe and > 10% improvement in LVEF is noticed at 12 months 
Quyyumi et al.  [26] USA / 2017 RCT   STEMI with a stent and LVEF ≤ 48% and ≥ four days post stent   161 Intracoronary infusion of autologous CD34 (+) cell  = 78   Placebo = 83 Six months with SPECT   Safe
Rodrigo et al. [27] Netherlands / 2013 CCT   First acute STEMI treated with PPCI and maximum CK level was > 1,600 U/L   54 MSC = 9 Standard therapy = 45 matched but nonrandomized patients Three, six months, one year, four-five years with Echocardiography, Holter, and clinical examination Improvements in LV function but not significantly different when compared to controls 
Roncalli et al. [28] France / 2011 RCT   Acute MI and successful reperfusion with LVEF ≤ 45%, age 18–75 years     101 BMMNC = 52   Placebo = 49 Three months with MRI, Echocardiography, and SPECT Multivariate analysis shows improvement of myocardial viability than univariate analysis  
San Roman et al.  [29] Spain / 2015 RCT   Adult, acute MI with PPCI or post-fibrinolysis PCI and rapamycin drug-eluting stent implantation   120 BMMNC = 30, GCSF = 30, G-CSF + cells = 29 Standard therapy = 31 12 months with cardiac MRI Not many differences among the four groups
Shah et al. [3] India / 2014 CT 30-70 years old, acute MI with PCI 19 Autologous BMCS = 12 Standard therapy = 7 24 months with Echocardiography, ECG, Holter monitoring Increase in LVEF with LV function improvements in stem cell group
Srimahachota et al. [30] Thailand / 2011 RCT H/o STEMI with LVEF < 50% and PCI 23 Autologous BMCs = 11 Standard therapy = 12 Six months with cardiac MRI Symptoms improved than baseline, but not many significant changes were noticed in the two groups
Sürder et al. [31] Switzerland / 2013 RCT Acute MI 200 BMMNC five-seven days after STEMI = 66, BMMNC three to four weeks after STEMI = 67 Standard therapy = 67 Four months with cardiac MRI No significant improvements
Traverse et al. [32] USA / 2012 RCT MI and PCI, LVEF < 45% 120 BMMNC at day three or day seven randomly = 79 Placebo = 41 Six months with cardiac MRI No significant improvement
Traverse et al. [33] USA / 2011 RCT Acute MI and PCI, LVEF < 45% 87 BMMNC after two to three weeks of MI = 58   Placebo = 29 Six months with cardiac MRI No significant improvement  
Traverse et al. [34] USA / 2018 RCT Patients of TIME trial, acute MI and PCI, LVEF < 45% 120 BMMNC at day three or day seven randomly = 79. 58 patients were followed up Placebo = 41, 27 patients were followed up Two years with cardiac MRI No significant improvement
Turan et al. [35] Germany / 2011 RCT   18-80 years old with MI and LV dysfunction 56 BMMNC = 38 Placebo = 18 Three, six months, and one year with left ventriculography Decrease in infarct size but an increase of global EF and infarct wall movement velocity in stem cell group  
Yerebakan et al. [36] Germany / 2011 RCT   MI at least 14 days before admission and LV akinesia with an indication for CABG 55 Intramyocardial CD133 (+) BMCs + CABG = 35 Only CABG = 20 18 months with 24-hour Holter monitoring, echocardiography, MRI, and CT scan Intramyocardial stem cell therapy was tolerable but did not have significant improvements