AUTHOR=Vervoorn Mats T. , Amelink Jantijn J. G. J. , Ballan Elisa M. , Doevendans Pieter A. , Sluijter Joost P. G. , Mishra Mudit , Boink Gerard J. J. , Bowles Dawn E. , van der Kaaij Niels P. 

TITLE=Gene therapy during ex situ heart perfusion: a new frontier in cardiac regenerative medicine?

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1264449

DOI=10.3389/fcvm.2023.1264449

ISSN=2297-055X

ABSTRACT=<p><italic>Ex situ</italic> organ preservation by machine perfusion can improve preservation of organs for transplantation. Furthermore, machine perfusion opens up the possibilities for selective immunomodulation, creation of tolerance to ischemia-reperfusion injury and/or correction of a pathogenic genetic defect. The application of gene modifying therapies to treat heart diseases caused by pathogenic mutations during <italic>ex situ</italic> heart perfusion seems promising, especially given the limitations related to delivery of vectors that were encountered during clinical trials using <italic>in vivo</italic> cardiac gene therapy. By isolating the heart in a metabolically and immunologically favorable environment and preventing off-target effects and dilution, it is possible to directly control factors that enhance the success rate of cardiac gene therapy. A literature search of PubMed and Embase databases was performed to identify all relevant studies regarding gene therapy during <italic>ex situ</italic> heart perfusion, aiming to highlight important lessons learned and discuss future clinical prospects of this promising approach.</p>