Development of an Improved Vascular Graft for use in Congenital Heart Surgery

Doctor's Name: 
Christopher Kane Breuer
Hospital/Institution: 
The Research Institute at Nationwide Children’s Hospital

This Grant is being funded by the Columbus Crew Soccer Foundation (Kirk Urso Memorial Fund)

Congenital cardiac anomalies represent the most common birth defect. Despite significant advances in the surgical and medical management of these anomalies; they remain a leading cause of death in the newborn period.  The most effective treatment for severe congenital heart disease is surgical reconstruction, unfortunately; the vast majority of reconstructive operations require the use of synthetic vascular grafts.  Complications arising from the use of currently available vascular conduits are a significant source of morbidity and mortality. The development of an improved vascular graft, specifically designed for use in congenital heart surgery, would over come a significant barrier to progress in the field, and holds great promise for improving the outcomes of infants requiring surgical intervention.

We have previously developed a new type of vascular graft specifically designed for use in children.  The graft is called a tissue engineered vascular graft and is made by seeding an individual’s own cells onto a biodegradable tube.  Over time the tube dissolves and a blood vessel grows in its place.  A tissue engineered vascular graft is a living vascular graft with growth potential which makes it particularly well suited for use in children.  We tested this vascular graft in a small clinical study evaluating its use in children undergoing congenital heart surgery.  Results of this study showed that the tissue engineered vascular graft worked well and grew when implanted in children, however; some of the grafts developed a narrowing over time, which is called stenosis.  All of the grafts that developed stenosis where successfully treated by dilating them using a special balloon using a technique called angioplasty. If we could overcome the problem of tissue engineered vascular graft narrowing, it would be an ideal vascular graft for use in children.

To this end we have developed animal models that help us to better understand how the tissue engineered vascular graft narrowing forms.  Using this model system we have determined that the narrowing is caused by accumulation or build up of smooth muscle cells in the lumen of the tissue engineered vascular graft.  Our studies have demonstrated that some of the smooth muscle cells are derived from the cells that normally line the inner surface of the tissue engineered vascular graft called endothelial cells.  The endothelial cells actually transform or turn into smooth muscle cells when they are exposed to a protein known as TGF-beta.  In our most recent set of experiments we determined that if you block the TGF-beta protein you can block the formation of tissue engineered vascular graft narrowing.

In this research proposal we want to test currently used medicine called losartan in order to see if it can prevent the formation of stenosis in the tissue engineered vascular graft.  Losartan is typically used to control blood pressure but has recently been discovered to also block the TGF-beta protein.  We will use our animal model to first see if losartan can stop stenosis in the short term and then see if short term use of losartan can block tissue engineered vascular graft narrowing for the long term.

We are currently performing the first clinical trial in the United States evaluating the use of tissue engineered vascular grafts in children undergoing congenital heart surgery.  Thus since the drug losartan is already approved for use in humans, if our experiments demonstrate that losartan blocks the formation of tissue engineered vascular graft narrowing without any serious side effects, we could rapidly start to test its use in children undergoing heart surgery.  The successful development of a strategy for preventing tissue engineered vascular graft stenosis would result in an improved vascular graft for use in children and improved our ability to treat patients with congenital heart disease.

 

 

Award Date 1: 
2014
Award Amount 1: 
$50,000
Award Date 2: 
2015
Award Amount 2: 
$50,000