Autologous CD133⁺ progenitor cell therapy as an adjunct to coronary artery bypass grafting in ischemic cardiomyopathy: a systematic review and meta-analysis

Ischemic cardiomyopathy remains a leading cause of cardiovascular mortality. Although autologous CD133⁺ progenitor cell therapy has been investigated as an adjunct to coronary artery bypass grafting (CABG), its clinical efficacy and safety remain uncertain. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of autologous CD133⁺ cell therapy administered during CABG in patients with ischemic cardiomyopathy. A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, Scopus, Google Scholar, and the Cochrane Library was conducted from database inception to January 2026. Eligible studies included randomized controlled trials and observational studies involving adults with ischemic cardiomyopathy in whom intraoperative administration of autologous CD133⁺ cells during CABG was compared with CABG alone. Random-effects meta-analyses were performed using maximum likelihood estimation with Hartung-Knapp adjustment. The certainty of evidence for critical and important outcomes was assessed using GRADE. Eleven studies encompassing 495 participants were included (7 RCTs, 4 cohort studies). No significant between-group difference was observed in MRI-assessed LVEF (MD − 1.34% [95% CI, − 9.09 to 6.41]; 4 studies), echocardiographic LVEF (MD 0.67% [95% CI, − 5.32 to 6.65]; 4 studies), or all-cause mortality (RR 0.88 [95% CI, 0.23 to 3.32]; 5 studies). MRI-derived LVESV showed no statistically significant reduction (MD − 21.57 mL [95% CI, − 67.07 to 23.92]; 2 studies). No significant between-group difference was observed in arrhythmia (RR 1.02 [95% CI, 0.68 to 1.54]; 2 studies; low certainty), and six-minute walk test results were highly imprecise, limiting clinical interpretability (MD 13.98 m [95% CI, − 530.79 to 558.76]; 2 studies; very low certainty). The certainty of evidence was very low or low across outcomes assessed with GRADE. Subgroup analysis by risk of bias demonstrated a statistically significant difference for MRI-assessed LVEF ( p = 0.008), with no benefit observed in low-risk-of-bias studies. Adjunctive autologous CD133⁺ cell therapy during CABG was not associated with consistent improvements in global left ventricular function or major clinical outcomes in ischemic cardiomyopathy. The certainty of evidence was very low across critical outcomes, and the LVESV finding should be considered exploratory and hypothesis-generating rather than confirmatory evidence of structural remodeling. Larger adequately powered randomized trials with standardized protocols are needed before this therapy can be recommended for routine clinical use.