Key result
AAV-mediated ZEB2, TMSB4, and PTMA delivery enhances pro-angiogenic changes and endothelial proliferation in preclinical models.
Why the study?
Preclinical cardiovascular models fail to recapitulate human cardiac physiology or are expensive and time-consuming, and living myocardial slices remain largely under-characterized.
Does AAV-mediated delivery of ZEB2, TMSB4, and PTMA induce similar pro-angiogenic and transcriptomic responses in living myocardial slices compared to a mouse model?
Does AAV-mediated delivery of ZEB2, TMSB4, and PTMA induce similar pro-angiogenic and transcriptomic responses in living myocardial slices compared to a mouse model?
Living myocardial slices from pigs represent a viable, functional ex vivo alternative to mouse models for testing cardiac pro-reparative gene therapies.
Porcine living myocardial slices offer a viable ex vivo alternative to mice; leaves open translation to human cardiac gene therapy.
Available models currently adopted for preclinical studies in the cardiovascular field either fail to recapitulate human cardiac physiology or are extremely expensive and time-consuming. Translational research would greatly benefit from the development of novel models that reflect the native mature phenotype of the human heart while being cost and time effective. Living myocardial slices (LMSs) have emerged as a novel, powerful ex vivo tool for translational research. Although the number of studies adopting LMSs is rapidly increasing, this model remains largely under-characterized. In this study, we make use of LMSs and compare them to a murine model to deliver the cardioprotective factor zinc finger E box-binding homeobox 2 (ZEB2), a transcription factor known to exert cardioprotective effects after ischemic injury and promote the secretion of pro-angiogenetic factors thymosin beta-4 (TMSB4) and prothymosin alpha (PTMA). Our data show that viral-mediated delivery of these factors induced similar cardiomyocyte gene expression changes in LMS and mouse models. We also show that the delivery of these pro-angiogenic factors enhances an angiogenic response in both models, indicating that LMSs are a suitable alternative to mice for studying the effects of gene transfer in various cardiac cell types.
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Caliandro et al. (2025) studied Preclinical model for cardiac gene therapy. AAV-mediated delivery of ZEB2, TMSB4, and PTMA vs. AAV-GFP was evaluated on Gene expression changes and endothelial cell proliferation. AAV-mediated delivery of ZEB2, TMSB4, and PTMA induced similar pro-angiogenic transcriptomic changes and enhanced endothelial cell proliferation in both porcine living myocardial slices and mice.
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