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Review
. 2023 Jan 12:9:981982.
doi: 10.3389/fcvm.2022.981982. eCollection 2022.

Cardiac regeneration: Options for repairing the injured heart

Jun Wang  1 , Meilin An  1 , Bernhard Johannes Haubner  2   3 , Josef M Penninger  1   4
Affiliations
Review

Cardiac regeneration: Options for repairing the injured heart

Jun Wang et al. Front Cardiovasc Med. .

Abstract

Cardiac regeneration is one of the grand challenges in repairing injured human hearts. Numerous studies of signaling pathways and metabolism on cardiac development and disease pave the way for endogenous cardiomyocyte regeneration. New drug delivery approaches, high-throughput screening, as well as novel therapeutic compounds combined with gene editing will facilitate the development of potential cell-free therapeutics. In parallel, progress has been made in the field of cell-based therapies. Transplantation of human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) can partially rescue the myocardial defects caused by cardiomyocyte loss in large animals. In this review, we summarize current cell-based and cell-free regenerative therapies, discuss the importance of cardiomyocyte maturation in cardiac regenerative medicine, and envision new ways of regeneration for the injured heart.

Keywords: cardiac regeneration; cell-based therapies; cell-free therapies; hPSC-CMs; transplantation.

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Conflict of interest statement

JP was the founder of Angios Biotech which develops blood vessel organoids for drug screening and clinical use in humans. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic of approaches for cardiac regenerative medicine using cell-free therapies. Mammals have the intrinsic capability to structurally and functionally regenerate their hearts shortly after birth, a capacity that is subsequently lost. Approaches to cardiac regeneration involve the re-entry of cardiomyocytes into the cell cycle and/or transdifferentiation of other resident cell types into cardiomyocytes. Recombinant proteins, RNA-based drugs, PROTAC, or small molecules could serve as viable strategies for cardiac repair. High-throughput screening of drug candidates can be performed in hPSC-CMs or, at lower throughput, cardiac organoids prior to clinical application. Created with BioRender.com.
FIGURE 2
FIGURE 2
Cell-based approaches to cardiac regenerative medicine. Delivery methods such as intracardiac injection and cell patches can be used for cell-based therapies. Though controversial, transplanting bone marrow-derived adult stem cells could promote cardiac function via secreted factors. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) can repair damaged hearts through tissue replacement of lost cardiomyocytes and help promote cardiac function by secreting growth factors such as VEGF. However, preclinical models and clinical trials must carefully address post-transplant arrhythmias and other side effects. The increased maturity of hPSC-CMs might reduce unwanted and potentially lethal arrhythmic events. Co-delivery of multiple cell types, including endothelial cells or other cardiac cell types, might improve hPSC-CMs retention and thereby promote the repair of injured hearts. Created with BioRender.com.
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References

    1. Heidenreich P, Bozkurt B, Aguilar D, Allen L, Byun J, Colvin M, et al. 2022 Aha/Acc/Hfsa guideline for the management of heart failure: a report of the American college of cardiology/American heart association joint committee on clinical practice guidelines. Circulation. (2022) 2022:1063. 10.1161/CIR.0000000000001063 - DOI - PubMed
    1. Piperata A, Caraffa R, Bifulco O, Avesani M, Apostolo A, Gerosa G, et al. Marginal donors and organ shortness: concomitant surgical procedures during heart transplantation: a literature review. J Cardiovasc Med. (2022) 23:167–75. 10.2459/jcm.0000000000001233 - DOI - PubMed
    1. Cui Y, Zheng Y, Liu X, Yan L, Fan X, Yong J, et al. Single-cell transcriptome analysis maps the developmental track of the human heart. Cell Rep. (2019) 26:1934–50e5. 10.1016/j.celrep.2019.01.079 - DOI - PubMed
    1. Lescroart F, Zaffran S. Single cell approaches to understand the earliest steps in heart development. Curr Cardiol Rep. (2022) 2022:1682. 10.1007/s11886-022-01681-w - DOI - PubMed
    1. Wang Q, Song Y, Chen J, Li Q, Gao J, Tan H, et al. Direct in vivo reprogramming with non-viral sequential targeting nanoparticles promotes cardiac regeneration. Biomaterials. (2021) 276:121028. 10.1016/j.biomaterials.2021.121028 - DOI - PubMed

Grants and funding

JP was supported by a Canada 150 Chair in Functional Genomics, a Paul G. Allen Distinguished Investigator Award, and the T. von Zastrow Foundation.

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