Development of an Unsupervised Classification with Multi-Level Analysis of the Heart Transplant Endomyocardial Biopsy

Purpose: Engineered heart tissue (EHT) implantation might be a promising future cardiac repair approach. Besides cell survival, electrical coupling plays a major role to support failing hearts. In this study we transplanted EHTs from human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) on cryo-injured guinea pig hearts and investigated their electrophysiological properties. Methods: Human iPSC were generated by retroviral reprogramming of dermal fibroblasts. Cardiac differentiation of hiPSC was performed by an embryoid body-based three-stage differentiation protocol. EHTs were created from hiPS-CM (5*106 cardiomyocytes and 2*106 hiPSC-endothelial cells per EHT). Left ventricular myocardial cryo-injury was induced in In Group 3, IL-6 levels were unchanged even after lungs were removed from circuit, suggesting that LF-trapped leukocytes did not contribute to increasing cytokine levels circulating in perfusate during EVLP. Conclusion: The potentially deleterious effects of LF-trapped leukocytes on lung grafts quality during EVLP appear to be limited while the cytokines storm stemming from lung grafts on EVLP can significantly impact their function. Our findings suggest the important role of leukocyte depletion or management in optimizing the lung grafts quality during EVLP.