Jabbour, R. J. et al. (2021) In vivo grafting of large engineered heart tissue patches for cardiac repair. JCI Insight, 6(15), e144068. (doi: 10.1172/jci.insight.144068) (PMID:34369384) (PMCID:PMC8410032)
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Abstract
Engineered heart tissue (EHT) strategies, by combining cells within a hydrogel matrix, may be a novel therapy for heart failure. EHTs restore cardiac function in rodent injury models, but more data are needed in clinically relevant settings. Accordingly, an upscaled EHT patch (2.5 cm × 1.5 cm × 1.5 mm) consisting of up to 20 million human induced pluripotent stem cell–derived cardiomyocytes (hPSC-CMs) embedded in a fibrin-based hydrogel was developed. A rabbit myocardial infarction model was then established to test for feasibility and efficacy. Our data showed that hPSC-CMs in EHTs became more aligned over 28 days and had improved contraction kinetics and faster calcium transients. Blinded echocardiographic analysis revealed a significant improvement in function in infarcted hearts that received EHTs, along with reduction in infarct scar size by 35%. Vascularization from the host to the patch was observed at week 1 and stable to week 4, but electrical coupling between patch and host heart was not observed. In vivo telemetry recordings and ex vivo arrhythmia provocation protocols showed that the patch was not pro-arrhythmic. In summary, EHTs improved function and reduced scar size without causing arrhythmia, which may be due to the lack of electrical coupling between patch and host heart.
| Item Type: | Articles |
|---|---|
| Additional Information: | We thank the British Heart Foundation (BHF) for funding this work through the BHF Centre for Regenerative Medicine (RM/17/1/33377). DJS is supported by a BHF intermediate basic science research fellowship (FS/15/33/31608 and an Medical Research Council project grant MR/R026416/1. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Dunne, Mr Michael and Myles, Dr Rachel and Smith, Professor Godfrey |
| Authors: | Jabbour, R. J., Owen, T. J., Pandey, P., Reinsch, M., Wang, B., King, O., Couch, L. S., Pantou, D., Pitcher, D. S., Chowdhury, R. A., Pitoulis, F. G., Handa, B. S., Kit-Anan, W., Perbellini, F., Myles, R. C., Stuckey, D. J., Dunne, M., Shanmuganathan, M., Peters, N. S., Siong Ng, F., Weinberger, F., Terracciano, C. M., Smith, G. L., Eschenhagen, T., and Harding, S. E. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | JCI Insight |
| Publisher: | American Society for Clinical Investigation |
| ISSN: | 2379-3708 |
| ISSN (Online): | 2379-3708 |
| Copyright Holders: | Copyright © 2021, Jabbour et al. |
| First Published: | First published in JCI Insight 6(15):e144068 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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