Project Details
Projekt
Ex vivo therapy of ischemic cardiomyopathy
Subject Area
Cardiac and Vascular Surgery
Term
from 2016 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 286251789
Ischemic cardiomyopathy (ICM) is one of leading causes of deathworldwide. Routine surgical methods, such as coronary bypassgrafting (e.g. total arterial revascularization, off-pump coronarysurgery) and functional myocardial reconstitution (e.g. ventricularpatch plasty) are ineffective to treat end stage ICM. The implantationof a ventricular assist device (VAD) or a heart transplantation are theonly therapeutic options in these patients. The combination ofextensive microsurgical coronary interventions and regenerativetherapy strategies may be a promising therapeutic approach.However, this technique cannot be performed in vivo. During the firstfunding period, general technical requirements for cardiac ex vivomicrosurgical procedures (e. g. extensive coronary endarterectomyand patch plasties) using the Organ Care System Heart (OCS Heart)were established and build the basis for the second funding period.Isolated cardiac (stem) cell therapies have not been shown toeffectively treat ischemic cardiomyopathy. To achieve clinicallysignificant improvements, tissue engineering strategies a likely tosurpass the effects of cell therapies alone and are a promisingapproach for translational applications. For this purpose, biologicalpatch materials are needed to reconstruct coronary arteries afterextensive endarterectomies and to reconstruct ventricular geometry.As currently available biological patch materials undergo cross-linkingand therefore are not vital tissue, they will degenerate within yearsafter implantation. Artificial materials (e.g. PE) are prothrombogenicand have a higher risk of infection. Therefore, there is a great need toinvent innovative, biofunctionalized patch materials, which have asufficient bio- and hemocompatibility for long term applications. Basedon our previous experiments on the OCS Heart and our data onbiofunctionalization of artificial materials, we will evaluate high-densityfibrin- and spider silk constructs as matrices for patch development.Patches will be endothelialized ex vivo in the OCS Heart based onestablished in vitro protocols. They will be used for extensive coronaryand myocardial ex vivo reconstructions. Tensile strength, endothelialadherence and immigration, biocompatibility and thrombogenicity willbe compared to commercially available patch materials. Retention ofthe endothelial cells will be evaluated under coronary perfusion.Finally, ex vivo treated hearts will be replanted and functionallyanalyzed.
DFG Programme
Clinical Research Units (Transfer Project)
Application Partner
TransMedics, Inc.
