Therapeutic Use of Stem Cells in the Management of Coronary Artery Disease and Heart Failure; Current Trends, Progress, and Challenges

Abstract

In recent years, stem cell therapy has been considered a novel therapy for human subjects with coronary artery disease and heart failure. While stem cells of different types have been successfully isolated in laboratory settings and transplanted into animal models, doubts still exist on the successful outcome of stem cell therapy for cardiomyocyte regeneration in human subjects who develop coronary artery disease and heart failure. Given the limited progress on stem cell therapy for this indication in human subjects, we aim to understand normal cardiomyocyte embryogenesis and apply it as a guide in identifying an ideal stem choice, critical growth, and transcription factors for cardiomyocyte regeneration as well as in the implementation of stem cell therapy for in human subjects with coronary artery disease and heart failure. Ethical limitations, safety, and long-term complications are critical in identifying the ideal stem cell choice. The route of infusion of the ideal stem cell, dose, and timing of administration must also be standardized for a favorable clinical outcome. All stem cell sources evaluated for this clinical indication in animal and human studies were associated with some level of structural remodeling and improved cardiac performance following infusion. In the search for and identification of the ideal stem cell type, ethical choices with limited complications of restenosis, arrhythmias, ischemic vasculopathy, graft rejection, and malignant transformation would therefore rank high for the successful implementation of the therapeutic use of stem cells in the management of coronary artery disease and heart failure in human subjects. Original research and review articles from March 1995 – March 2022 were searched online. Search engines included Google Scholar, PubMed, Web of Science, and National Institute of Health. The keywords for the literature search included the use of stem cells for treatment, stem cell therapy, coronary artery disease, coronary heart disease, ischemic heart disease, and heart failure. Manual searches were also conducted for articles related to the pool generated from the online search. Statistical data were obtained from American Heart Association, Center for Disease Control (CDC), World Health Organization (WHO), and clinicaltrials.gov. From the articles generated, relevant sections were reviewed to understand the progress made with the therapeutic use of stem cells for managing coronary artery disease and heart failure in human subjects. The sources of stem cells, transcription factors, isolation methods, routes, and timing of infusion of different stem cell types evaluated for this clinical indication in preclinical and clinical studies were reviewed and outlined. The clinical outcomes of using different types of stem cells from both studies were also reviewed and compared, as well as ethical limitations, study limitations, and resultant adverse effects.