Immature human engineered heart tissues engraft in a guinea pig chronic injury model.
Constantin von BibraAya ShibamiyaAndrea BährBirgit GeertzMaria KöhneTim StuedemannJutta StarbattyVerena Horneffer-van der SluisUlrich C KlostermeierNadja HornaschewitzXinghai LiEckhard WolfNikolai KlymiukMarkus KraneChristian KupattBernhard HieblThomas EschenhagenFlorian WeinbergerPublished in: Disease models & mechanisms (2023)
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.
Keyphrases
- cell therapy
- left ventricular
- endothelial cells
- induced apoptosis
- clinical trial
- heart failure
- cell cycle arrest
- high glucose
- stem cells
- mitral valve
- high resolution
- pulmonary hypertension
- cell death
- acute myocardial infarction
- cell proliferation
- drug induced
- left atrial
- randomized controlled trial
- endoplasmic reticulum stress
- mass spectrometry
- hypertrophic cardiomyopathy
- open label
- ejection fraction