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

Frontiers in Cardiovascular Medicine

Cardiovascular Medicine

Gerard J. J. Boink¹  Jantijn J. G. J. Amelink²  Niels P. van der Kaaij²  Mats T. Vervoorn²  Elisa M. Ballan³  Dawn E. Bowles⁴  Mudit Mishra⁵  Joost P. G. Sluijter⁶  Pieter A. Doevendans⁷ 

[1] Amsterdam Cardiovascular Sciences, Department of Medical Biology, Amsterdam University Medical Centers, Amsterdam, Netherlands;Amsterdam Cardiovascular Sciences, Department of Cardiology, Amsterdam University Medical Centers, Amsterdam, Netherlands;Division of Heart & Lungs, Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, Netherlands;Division of Heart & Lungs, Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, Netherlands;Laboratory of Experimental Cardiology, Division Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands;Netherlands Heart Institute, Utrecht, Netherlands;Divison of Surgical Sciences, Department of Surgery, Duke University School of Medicine, Durham, NC, United States;Laboratory of Experimental Cardiology, Division Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands;Laboratory of Experimental Cardiology, Division Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands;Regenerative Medicine Utrecht, Circulatory Health Research Center, University Utrecht, Utrecht, Netherlands;Netherlands Heart Institute, Utrecht, Netherlands;Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht, Netherlands;

关键词: gene therapy;    heart transplantation (HTx);    heart failure;    regenerative medicine;    ex situ;   

DOI  :  10.3389/fcvm.2023.1264449

 received in 2023-07-20, accepted in 2023-10-02,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
© 2023 Vervoorn, Amelink, Ballan, Doevendans, Sluijter, Mishra, Boink, Bowles and van der Kaaij.