Tissue Engineered Blood Vessels
The Truskey Lab has developed a method of rapidly synthesizing perfusable tissue-engineered vascular constructs made from human cells. These tissue-engineered blood vessels (TEBVs) are similar in size and structure to human arterioles. They provide a robust platform for studying the circulatory system in vitro. In particular, our research focuses cardiovascular aging, vascular inflammation, disease modeling, and drug testing.
Progeria Disease Modeling and Drug Testing
The accelerated aging disease, Hutchinson-Gilford Progeria syndrome (HGPS), is a rare disorder caused by a mutation in the LMNA gene that leads to a truncated and farnesylated form of the protein progerin. This condition primarily affects cells of the mesenchymal lineage, which ultimately manifests as patients appearing significantly older than they are (alopecia, growth retardation, decreased bone density, etc.). The primary cause of death of those suffering from HGPS is atherosclerosis occurring at 10-15 years of age. This indicates that blood vessels, particularly vascular smooth muscle cells, are key sites where the disorder is manifested. We aim to build on our previous work with tissue engineered blood vessels by using induced pluripotent stem-cell derived vascular smooth muscle cells from Progeria patients in the fabrication of vascular constructs. This will allow us to replicate the disorder’s effects on the circulatory system in vitro. This will provide a valuable platform for both improving understanding of Progeria and testing treatments for Progeria.
A Tissue Engineered Blood Vessel (TEBV) model for endothelial radiation injury
There exists an important knowledge gap in the mechanistic understanding of the pathways involved in cardiovascular dysfunction after radiation exposure. For example, years after occupational radiation exposure, as well as medical radiation exposure (i.e. therapeutic radiation in oncology) there appears to be a higher rate of cardiovascular mortality. While there is a general idea that the endothelium and endothelial injury and dysfunction play an important role after radiation exposure, the understanding of that process is greatly limited. We are using the TEBV system as a high throughput, controlled ex vivo environment to further study and characterize radiation injury to the endothelium, as well as collaborating with the Bowles lab for in vivo validation using an animal radiation model.