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Review
. 2023 May:178:51-58.
doi: 10.1016/j.yjmcc.2023.03.008. Epub 2023 Mar 23.

Direct cardiac reprogramming: A new technology for cardiac repair

Paige E Brlecic  1 , Clark A Bonham  1 , Todd K Rosengart  1 , Megumi Mathison  2
Affiliations
Review

Direct cardiac reprogramming: A new technology for cardiac repair

Paige E Brlecic et al. J Mol Cell Cardiol. 2023 May.

Abstract

Cardiovascular disease is one of the leading causes of morbidity and mortality worldwide, with myocardial infarctions being amongst the deadliest manifestations. Reduced blood flow to the heart can result in the death of cardiac tissue, leaving affected patients susceptible to further complications and recurrent disease. Further, contemporary management typically involves a pharmacopeia to manage the metabolic conditions contributing to atherosclerotic and hypertensive heart disease, rather than regeneration of the damaged myocardium. With modern healthcare extending lifespan, a larger demographic will be at risk for heart disease, driving the need for novel therapeutics that surpass those currently available in efficacy. Transdifferentiation and cellular reprogramming have been looked to as potential methods for the treatment of diseases throughout the body. Specifically targeting the fibrotic cells in cardiac scar tissue as a source to be reprogrammed into induced cardiomyocytes remains an appealing option. This review aims to highlight the history of and advances in cardiac reprogramming and describe its translational potential as a treatment for cardiovascular disease.

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Conflict of interest statement

Disclosure: “TKR is a board member, consultant and holds a significant financial interest with Xylocor Therapeutics, LLC and also receives royalty payments for intellectual property held by Cornell University and Baylor College of Medicine relevant to this work. He serves on the scientific advisory board for PLX Pharma, Inc. for which he holds a significant equity interest. He is also a board member of the American Association for Thoracic Surgery and in this role serves as a representative to the Board of Governors of the American College of Surgeons.

Figures

Figure 1.
Figure 1.. Timeline of Cardiac Reprogramming
Timeline depicting the history of and key studies in the development of reprogramming cardiac fibroblasts into iCMs. Abbreviations: GMT: Gata4 (G), Mef2c (M), Tbx5 (T) cocktail, iCM: Induced cardiomyocyte-like cell, shRNA: Small hairpin RNA, NGS: Next generation sequencing, TB4: Thymosin β4, GHMT: GMT + Hand2 (H) factor, VEGF: Vascular endothelial growth factor, MiRNA: MicroRNA, Poly: Polycistronic, Ad GMT: Adenovirus administrated GMT, TGFB: Transforming growth factor β, AAV: Adeno-associated virus, AuNPs: Gold nanoparticles, SeV: Sendai virus
Figure 2.
Figure 2.. Routes of Delivery
a. Catheter-based coronary artery injection. b. Catheter-based coronary sinus injection. c. Catheter-based Trans-AV Approach for Direct Myocardial Injection. d. Catheter-based Transseptal Approach for Direct Myocardial Injection. e. Surgical Mini-thoracotomy Approach for Direct Myocardial Injection. f. Surgical Closed Chest Totally Endoscopic/Robotic Approach for Direct Myocardial Injection. g. Surgical Sternotomy Approach for Direct Myocardial Injection. AV, aortic valve.
See this image and copyright information in PMC

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