TY - JOUR
T1 - Gene therapy during ex situ heart perfusion
T2 - a new frontier in cardiac regenerative medicine?
AU - Vervoorn, Mats T.
AU - Amelink, Jantijn J. G. J.
AU - Ballan, Elisa M.
AU - Doevendans, Pieter A.
AU - Sluijter, Joost P. G.
AU - Mishra, Mudit
AU - Boink, Gerard J. J.
AU - Bowles, Dawn E.
AU - van der Kaaij, Niels P.
N1 - Funding Information: This study was funded by the Regenerative Medicine Crossing Borders (RegMed XB) public-private partnership, the Leducq Transatlatic Network of Excellence to Cure Phosphlamban-Induced Cardiomyopathy (CURE-PLaN), the Pluripotent Stem Cells for Inherited Diseases and Embryonic Research (PSIDER) program (ZonMW), the Heart Vector-mediated Gene Therapy (HARVEY) project [Dutch Research Council (NWO)] and GERMY (Horizon EU). Publisher Copyright: 2023 Vervoorn, Amelink, Ballan, Doevendans, Sluijter, Mishra, Boink, Bowles and van der Kaaij.
PY - 2023
Y1 - 2023
N2 - Ex situ 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 ex situ heart perfusion seems promising, especially given the limitations related to delivery of vectors that were encountered during clinical trials using in vivo 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 ex situ heart perfusion, aiming to highlight important lessons learned and discuss future clinical prospects of this promising approach.
AB - Ex situ 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 ex situ heart perfusion seems promising, especially given the limitations related to delivery of vectors that were encountered during clinical trials using in vivo 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 ex situ heart perfusion, aiming to highlight important lessons learned and discuss future clinical prospects of this promising approach.
KW - ex situ heart perfusion
KW - gene therapy
KW - heart failure
KW - heart transplantation (HTx)
KW - regenerative medicine
UR - http://www.scopus.com/inward/record.url?scp=85175374058&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fcvm.2023.1264449
DO - https://doi.org/10.3389/fcvm.2023.1264449
M3 - Review article
C2 - 37908499
SN - 2297-055X
VL - 10
JO - Frontiers in cardiovascular medicine
JF - Frontiers in cardiovascular medicine
M1 - 1264449
ER -