Stem cell therapy for non-ischemic dilated cardiomyopathy: a systematic review and meta-analysis

Abstract

BackgroundStem cell therapy is the transplantation of human cells to aid the healing of damaged or wounded tissues and cells. Only a few small-scale trials have been conducted to investigate stem cell therapy for non-ischemic dilated cardiomyopathy (DCM). We aimed to perform a systematic review and meta-analysis to assess the efficacy and safety of stem cell therapy for DCM.MethodsA comprehensive search of the databases of PubMed, Embase, Web of Science Core Collection, Cochrane Library, and ProQuest was conducted from their inception to June 30, 2024, to access randomized controlled trials (RCTs) that were centered on stem cell therapy for DCM. The primary outcome was left ventricular ejection fraction (LVEF), and the secondary outcomes included left ventricular end-diastolic dimension (LVEDD), left ventricular end-diastolic volume (LVEDV), 6-min walk test (6MWT), NYHA functional classification, quality of life (QoL) such as Minnesota Living with Heart Failure Questionnaire (MLHFQ) and Kansas City Cardiomyopathy Questionnaire (KCCQ), N-terminal pro-brain natriuretic peptide (NT-proBNP), and VO2 peak. Moreover, major adverse cardiovascular events (MACEs) were also recorded. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of the included RCTs, and the certainty of the evidence was assessed using the GRADE method. Sensitivity analysis was taken into consideration to determine the stability of the results. This review was registered with PROSPERO (CRD42024568912).ResultsEleven RCTs involving 637 participants were included in the quantitative analysis. The results indicated that there was a significant increase in mean LVEF (MD = 4.84, 95% CI 3.25–6.42, P < 0.00001) and considerable decrease in LVEDV (MD = − 29.51, 95% CI − 58.07 to − 0.95, P = 0.04) and NT-proBNP (MD = − 737.55, 95% CI − 904.28 to − 570.82, P < 0.00001) in DCM patients treated with stem cell therapy compared with controls. Stem cell therapy was also related to the improvement in functional capacity, as evaluated by 6MWT (MD = 44.32, 95% CI 34.70 − 53.94, P < 0.00001) and NYHA functional classification (MD = − 0.63, 95% CI − 0.96 to − 0.30, P = 0.0002). It also had positive effects on improving QoL, including significantly decreasing MLHFQ score (MD = − 16.60, 95% CI − 26.57 to − 6.63, P = 0.001) and increasing the KCCQ score (MD = 14.76, 95% CI 7.76 − 21.76, P < 0.0001). No significant differences were observed in LVEDD, VO2 peak, and MACEs between the two groups. The GRADE analysis revealed that the evidence was graded from low to moderate. Sensitivity analysis of the results suggested that the results were stable.ConclusionThe systematic review and meta-analysis indicates that stem cell therapy may be an effective and safe approach to improve cardiac function and quality of life in DCM patients. Nevertheless, given the limitations of existing studies, larger well-designed RCTs are required to confirm and support our findings.