Immature human engineered heart tissues engraft in a guinea pig chronic injury model
Summary
Engineered heart tissue (EHT) transplantation represents an innovative, regenerative approach for heart failure patients. Late preclinical trials are underway, and a first clinical trial started recently. Preceding studies revealed functional recovery after implantation of in vitro-matured EHT in the subacute stage, whereas transplantation in a chronic injury setting was less efficient. When transplanting matured EHTs, we noticed that cardiomyocytes undergo a dedifferentiation step before eventually forming structured grafts. Therefore, we wanted to evaluate whether immature EHT (EHTIm) patches can be used for transplantation. Chronic myocardial injury was induced in a guinea pig model. EHTIm (15×106 cells) were transplanted within hours after casting. Cryo-injury led to large transmural scars amounting to 26% of the left ventricle. Grafts remuscularized 9% of the scar area on average. Echocardiographic analysis showed some evidence of improvement of left-ventricular function after EHTIm transplantation. In a small translational proof-of-concept study, human scale EHTIm patches (4.5×108 cells) were epicardially implanted on healthy pig hearts (n=2). In summary, we provide evidence that transplantation of EHTIm patches, i.e. without precultivation, is feasible, with similar engraftment results to those obtained using matured EHT. © 2023. Published by The Company of Biologists Ltd.
| Authors | von Bibra C, Shibamiya A, Bähr A, Geertz B, Köhne M, Stuedemann T, Starbatty J, Horneffer-van der Sluis V, Klostermeier UC, Hornaschewitz N, Li X, Wolf E, Klymiuk N, Krane M, Kupatt C, Hiebl B, Eschenhagen T, Weinberger F |
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| Journal | Disease models & mechanisms |
| Publication Date | 2023 May 1;16(5) |
| PubMed | 37272385 |
| PubMed Central | PMC10259837 |
| DOI | 10.1242/dmm.049834 |