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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Apr 26, 2021; 13(4): 236-259
Published online Apr 26, 2021. doi: 10.4252/wjsc.v13.i4.236
Stem cell therapy for heart failure: Medical breakthrough, or dead end?
Mathieu Rheault-Henry, Ian White, Diya Grover, Rony Atoui
Mathieu Rheault-Henry, Ian White, Northern Ontario School of Medicine, Sudbury P3E 2C6, Ontario, Canada
Diya Grover, Ross University School of Medicine, St. Michael BB11093, Barbados
Rony Atoui, Division of Cardiac Surgery, Health Sciences North, Northern Ontario School of Medicine, Sudbury P3E 3Y9, Ontario, Canada
Author contributions: Rheault-Henry M, White I, Grover D collected the data and contributed to the writing of the manuscript; Atoui R devised the project, developed the main conceptual ideas and edited the manuscript; all authors revised and approved the final version.
Conflict-of-interest statement: We have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Rony Atoui, MSc, MD, FACS, Cardiac Surgeon, Division of Cardiac Surgery, Health Sciences North, Northern Ontario School of Medicine, 865 Regent Street, Suite 301, Sudbury P3E 3Y9, Ontario, Canada. rony.atoui@gmail.com
Received: October 30, 2020
Peer-review started: October 30, 2020
First decision: November 30, 2020
Revised: December 22, 2020
Accepted: March 22, 2021
Article in press: March 22, 2021
Published online: April 26, 2021
Abstract

Heart failure continues to be one of the leading causes of morbidity and mortality worldwide. Myocardial infarction is the primary causative agent of chronic heart failure resulting in cardiomyocyte necrosis and the subsequent formation of fibrotic scar tissue. Current pharmacological and non-pharmacological therapies focus on managing symptoms of heart failure yet remain unable to reverse the underlying pathology. Heart transplantation usually cannot be relied on, as there is a major discrepancy between the availability of donors and recipients. As a result, heart failure carries a poor prognosis and high mortality rate. As the heart lacks significant endogenous regeneration potential, novel therapeutic approaches have incorporated the use of stem cells as a vehicle to treat heart failure as they possess the ability to self-renew and differentiate into multiple cell lineages and tissues. This review will discuss past, present, and future clinical trials, factors that influence stem cell therapy outcomes as well as ethical and safety considerations. Preclinical and clinical studies have shown a wide spectrum of outcomes when applying stem cells to improve cardiac function. This may reflect the infancy of clinical trials and the limited knowledge on the optimal cell type, dosing, route of administration, patient parameters and other important variables that contribute to successful stem cell therapy. Nonetheless, the field of stem cell therapeutics continues to advance at an unprecedented pace. We remain cautiously optimistic that stem cells will play a role in heart failure management in years to come.

Keywords: Stem cells, Heart failure, Myocardial infarction, Regeneration, Remodeling, Ethical issues

Core Tip: Cellular based therapeutics have emerged as a promising potential option for the treatment of heart failure. To date, there have been numerous clinical trials evaluating safety, efficacy and feasibility of the use of adult and pluripotent stem cells in the treatment of chronic cardiomyopathy. Although clinical results have varied, important lessons have been learned about the optimal cell type, route of administration and the implementation of tissue engineering.