Stem cell therapy for acute myocardial infarction: Mesenchymal Stem Cells and induced Pluripotent Stem Cells

ABSTRACT

Introduction

Acute myocardial infarction (AMI) remains a leading cause of death in the United States. The limited capacity of cardiomyocytes to regenerate and the restricted contractility of scar tissue after AMI are not addressed by current pharmacologic interventions. Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach due to their low antigenicity, ease of harvesting, and efficacy and safety in preclinical and clinical studies, despite their low survival and engraftment rates. Other stem cell types, such as induced pluripotent stem cells (iPSCs) also show promise, and optimizing cardiac repair requires integrating emerging technologies and strategies.

Areas covered

This review offers insights into advancing cell-based therapies for AMI, emphasizing meticulously planned trials with a standardized definition of AMI, for a bench-to-bedside approach. We critically evaluate fundamental studies and clinical trials to provide a comprehensive overview of the advances, limitations and prospects for cell-based therapy in AMI.

Expert opinion

MSCs continue to show potential promise for treating AMI and its sequelae, but addressing their low survival and engraftment rates is crucial for clinical success. Integrating emerging technologies such as pluripotent stem cells and conducting well-designed trials will harness the full potential of cell-based therapy in AMI management. Collaborative efforts are vital to developing effective stem cell therapies for AMI patients.

KEYWORDS:

• Acute myocardial infarction
• mesenchymal stem cells
• induced pluripotent stem cells
• cell-based therapy
• cardiac repair
• precision medicine
• exosomes

Article highlights

• AMI ranks as a primary contributor to mortality in the United States. With ischemia, injured myocardium prompts an inflammatory response that is followed by tissue repair and cardiac remodeling processes leading to heart failure.

• The therapeutic actions of MSCs are primarily due to paracrine-mediated effects rather than by their capacity to engraft and structurally repair the myocardium.

• MSCs are immune evasive, pro-angiogenic and anti-fibrotic, ideal characteristics for cardiovascular regenerative medicine.

• To achieve efficient cell-based therapies, promoting cell survival and engraftment at the ischemic area is crucial to contain cardiac remodeling and to preserve cardiac hemodynamic performance.

• iPSCs can be reprogrammed from somatic cells into a pluripotent state, and can differentiate into any cell type, including all cardiac lineages.

• In preclinical trials, iPSC-derived cardiomyocytes improve cardiac function and reduce infarct size. Further studies are needed to optimize their safety and efficacy.

• The MSC secretome has significant potential for translation into cell-free biotherapies as off-the-shelf-products.

• Combining cell-based regenerative therapy with precision medicine approaches will maximize efficacy, minimize adverse effects, and reduce costs by avoiding ineffective therapies.

Declaration of interest

JM Hare reported having a patent for cardiac cell-based therapy. He holds equity in Vestion Inc. and maintains a professional relationship with Vestion Inc. as a consultant and member of the Board of Directors and Scientific Advisory Board. JM Hare is the Chief Scientific Officer, a compensated consultant and advisory board member for Longeveron, and holds equity in Longeveron. He is also the co-inventor of intellectual property licensed to Longeveron. Longeveron LLC and Vestion Inc. did not participate in funding this work. JM Hare’s relationships are disclosed to the University of Miami, and a management plan is in place. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by National Heart, Lung, and Blood Institute (grant 1R01HL134558-01) and U.S. Department of Defense (grant W81XWH-19-PRMRP-CTA).