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Review
. 2022 May;24(5):473-486.
doi: 10.1007/s11886-022-01668-7. Epub 2022 Mar 5.

A Change of Heart: Human Cardiac Tissue Engineering as a Platform for Drug Development

Samantha B Bremner  1   2 , Karen S Gaffney  1 , Nathan J Sniadecki  1   3   4   5   2 , David L Mack  6   7   8
Affiliations
Review

A Change of Heart: Human Cardiac Tissue Engineering as a Platform for Drug Development

Samantha B Bremner et al. Curr Cardiol Rep. 2022 May.

Abstract

Purpose of review: Human cardiac tissue engineering holds great promise for early detection of drug-related cardiac toxicity and arrhythmogenicity during drug discovery and development. We describe shortcomings of the current drug development pathway, recent advances in the development of cardiac tissue constructs as drug testing platforms, and the challenges remaining in their widespread adoption.

Recent findings: Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been used to develop a variety of constructs including cardiac spheroids, microtissues, strips, rings, and chambers. Several ambitious studies have used these constructs to test a significant number of drugs, and while most have shown proper negative inotropic and arrhythmogenic responses, few have been able to demonstrate positive inotropy, indicative of relative hPSC-CM immaturity. Several engineered human cardiac tissue platforms have demonstrated native cardiac physiology and proper drug responses. Future studies addressing hPSC-CM immaturity and inclusion of patient-specific cell lines will further advance the utility of such models for in vitro drug development.

Keywords: Cardiac tissue engineering; Cardiotoxicity; Drug screening; Pluripotent stem cells.

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Conflict of interest statement

Samantha B. Bremner reports grants from National Science Foundation Graduate Research Fellowship (Grant No. DGE-1762114), during the conduct of the study. Karen S. Gaffney has nothing to disclose. Nathan J. Sniadecki reports grants from the National Science Foundation (CMMI-1824792), National Institutes of Health (HL149734, TR003519, DE029827), and Sana Biotechnology during the conduct of the study and others from Curi Bio and Stasys Medical outside the submitted work. In addition, Dr. Sniadecki has a patent US20190029549A1 “System for magnetic detection of myocardial forces” licensed to Curi Bio. David L. Mack reports grants from Institute for Stem Cell and Regenerative Medicine Innovation Pilot Award, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center P50AR065139, and Jesse’s Journey Foundation, during the conduct of the study, and others from Curi Bio, Inc. and Kinea Bio, Inc., outside the submitted work.

Figures

Fig. 1
Fig. 1
Different engineered cardiac tissue platforms organized by relative throughput and biological relevance with a description of their advantages and limitations
See this image and copyright information in PMC

References

    1. Wouters OJ, McKee M, Luyten J. Estimated research and development investment needed to bring a new medicine to market, 2009–2018. J Am Med Assoc. 2020;323(9):844–853. doi: 10.1001/jama.2020.1166. - DOI - PMC - PubMed
    1. Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics. 2019;20(2):273–286. doi: 10.1093/biostatistics/kxx069. - DOI - PMC - PubMed
    1. Packer M. Unbelievable folly of clinical trials in heart failure. Circ Hear Fail. 2016;9(4). 10.1161/CIRCHEARTFAILURE.116.002837. - PubMed
    1. Hartung T. Look back in anger - what clinical studies tell us about preclinical work. Altex. 2013;30(3):275–291. doi: 10.14573/altex.2013.3.275. - DOI - PMC - PubMed
    1. Olson H, Betton G, Robinson D, Thomas K, Monro A, Kolaja G, et al. Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol. 2000;32(1):56–67. doi: 10.1006/rtph.2000.1399. - DOI - PubMed

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