Abstract
Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds. Because the precise mechanisms regulating this process are still under investigation, inducible genetic mouse models are an important and widely used research tool. However, here we describe the importance of challenging the baseline assumption that tamoxifen is inert when used as a small molecule inducer in the context of cardiovascular tissue engineering. Employing a standard inferior vena cava vascular interposition graft model in C57BL/6 mice, we discovered differences in the immunologic response between control and tamoxifen-treated animals, including occlusion rate, macrophage infiltration and phenotype, the extent of foreign body giant cell development, and collagen deposition. Further, differences were noted between untreated males and females. Our findings demonstrate that the host-response to materials commonly used in cardiovascular tissue engineering is sex-specific and critically impacted by exposure to tamoxifen, necessitating careful model selection and interpretation of results.
Highlights
Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds
Two weeks was chosen as the study end date as we have previously reported this as a key time point for determining long-term Tissue engineered vascular grafts (TEVGs) outcomes in mice[28]
Improving our understanding of the biomechanical, cellular, and molecular pathways underlying neotissue formation in TEVGs holds the key to improving their performance through rational design
Summary
Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds. Tissue engineered vascular grafts (TEVGs) represent a promising development in vascular s urgery[1] These polymer-based conduits degrade over time and are replaced by native tissue, resulting in the formation of a functional blood vessel made from the patient’s own cells. Genetic mouse models are a powerful tool to study these processes because of their ability to manipulate cellular pathways both temporally, through the use of tamoxifen- and diphtheria-induced models, and spatially, through the use of cell-specific models[2,3,4]. A selective estrogen receptor modulator, has wide-spread use as a small molecule effector for inducible knock-out m odels[5]. This system works by fusing a Cre-recombinase to an estrogen receptor ( CreERT2) that resides in the cytosol until activated. Selective estrogen receptor modulators such as tamoxifen are known to have variable tissue-specific effects, acting as an antagonist in breast tissue, but as a partial agonist
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
