Stem cell implants for the treatment of ischemic cardiomyopathy: a systematic review and meta-analysis

Introduction: Cardiovascular diseases are the main causes of global mortality. Adverse cardiac remodeling after AMI often results in heart failure, even with therapeutic advances such as primary angioplasty. In this context, regenerative therapies emerge, such as the use of stem cells and biological grafts, to promote tissue regeneration and prevent ventricular remodeling. Objectives: To investigate stem cell implants in the treatment of ischemic cardiomyopathy. Methods: This systematic review included controlled clinical trials and experimental studies published between 2013 and September 2023 that evaluated stem cell implants for cardiac regeneration in ischemic cardiomyopathy. Searches were conducted in PubMed, LILACS, and SciELO databases in English, Spanish, and Portuguese. Reviews, case reports, narrative reviews, and studies without a control group were excluded. Risk of bias was assessed using the Joanna Briggs Institute checklist. Study selection followed PRISMA guidelines, and data were analyzed using OpenMetaAnalyst software. Results: Initially, 41 studies were identified and after applying the inclusion and exclusion criteria, only 6 remained for the final analysis, which had a sample space of 397 participants. The studies analyzed variables such as mortality, proBNT, LVEF, and infarction rate and demonstrated safety of the intervention and modest improvement in ventricular ejection fraction with the use of stem cells, but without significant impact on long-term clinical outcomes. Discussion: This systematic review evaluated the use of bone marrow-derived cells (BMCs) in cardiac regeneration in patients with ischemic heart failure and STEMI. Studies suggest modest improvement in cardiac function, favorable ventricular remodeling, and reduction of heart failure biomarkers after intramyocardial administration of the cells. Some cell phenotypes, such as CD31+ and CD45+CD31+, showed an association with greater reduction in infarct size. However, the results were heterogeneous and not always statistically significant. The main limitations included small sample size, lack of standardization of protocols, and methodological variability. Furthermore, there was no consistent impact on robust clinical outcomes such as mortality and rehospitalization. Despite this, cell therapy shows potential as a complementary strategy in the treatment of advanced heart failure, and larger multicenter studies are needed to confirm its clinical efficacy. Conclusion: Bone marrow-derived cell (BMC) therapy is a promising approach for ischemic heart failure and STEMI, showing potential to improve cardiac function, especially with certain cell subtypes. However, the heterogeneity of the results and the lack of consistent impact on primary outcomes limit its clinical application. Progress depends on better standardization of protocols and personalized strategies for each group of interest evaluated, and further studies and with a larger sample size are needed to possibly consolidate this therapy as a routine practice in cardiology.