Hydrojet-Based Delivery of IPSC-Derived Autologous Cardiomyocytes into the Myocardium

Objectives: Myocardial infarction leads to the damage of cardiomyocytes due to the lack of oxygen and nutrient delivery to the myocardium. The missing cardiomyocytes cannot be replaced by the proliferation of remaining cardiomyocytes, which results in heart failure. A promising strategy to replace the damaged and lost cardiomyocytes and to improve the functionality of the heart is the transplantation of iPSC-derived autologous cardiomyocytes into the infarcted myocardium. In this study, the delivery of footprint-free cardiomyocytes generated from iPSCs was tested using standard needle application and Hydrojet method.

Methods: Different pressures were tested for the delivery of microparticles (10 µm) into ex vivo porcine hearts. Post-application, the distribution of particles in the myocardium was detected and analyzed using magnetic resonance imaging. Then, the cardiomyocytes were labeled with a near-infrared fluorescent dye and applied into the myocardium. The cells in the myocardium were detected using an in vivo imaging system.

Result: Our proof of principle studies demonstrated that the Hydrojet-based application can be applied to successfully deliver cardiomyocytes into the myocardium. Compared with the needle application, the cardiomyocytes were widely distributed in the myocardium using the Hydrojet device and less undesired distribution of the cells via blood vessels was discovered.

Conclusion: The successful delivery of iPSC-derived cardiomyocytes into the myocardium of ex vivo porcine hearts was shown using Hydrojet application. In our next studies, cardiomyocytes will be delivered in a pig myocardial infarction model and analyzed regarding the integration of iPSC-derived cardiomyocytes and the influence on ejection fraction. Further improvements are also planned toward minimal invasive myocardial delivery using Hydrojet method.

Publication History

Article published online:
19 February 2021