RESUMEN
Cell therapy, gene therapy, and tissue engineering have been explored as potential strategies to repair or regenerate damaged cardiac tissue. Despite the presence of encouraging preclinical data, clinical trials of regenerative cardiac therapies have yielded mixed results. Our study aimed to investigate the fate of all registered clinical trials within regenerative cardiac medicine, with the purpose of exploring the potential role of publication bias (or trial-completion bias), how published and unpublished research affects the field, and to draw lessons and recommendations for future clinical trials. In this analysis, we show that only a third of all registered trials has yielded results and that a significant number of trials are not completed. Furthermore, we identified significant heterogeneity in study design, study phase, funding, specific therapies used, primary outcome measures and methods of outcome assessment. These observations might hinder the successful translation of cardiac regenerative therapies into clinical practice.
RESUMEN
Hypothermic oxygenated perfusion (HOPE) is an emerging technique for donor heart preservation that is currently being studied in multiple clinical trials with promising results. When compared to HOPE for other organs, cardiac protocols involve red blood cell (RBC) supplementation, despite absence of comparative evidence for its benefits. In this perspective paper, we discuss the pros and cons of the addition of RBC's during cardiac HOPE. Although the current clinical results with RBC supplementation during HOPE seem promising, potential downsides of RBC supplementation cannot be ruled out. The impact of supplemented RBC's during cardiac HOPE requires further investigation to improve HOPE protocols, in order to optimize heart preservation using this promising technology.
RESUMEN
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.