Abstract 12382: Evaluation of Tissue Engineered Human Acellular Vessels as a Blalock-Taussig-Thomas Shunt in a Juvenile Primate Model

Abstract

Cyanotic congenital heart disease (CCHD) due to one or more structural abnormalities causes insufficient blood oxygenation. Approximately 2 out of every 1000 infants are born with CCHD and palliative treatment for many patients involves shunting blood from the systemic to the pulmonary circuits, often through a modified Blalock-Taussig-Thomas shunt (BTTs). Synthetic vascular grafts typically used for BTTs have associated risks for intimal hyperplasia, thrombosis, and infection. Humacyte, Inc. has developed a 6mm diameter tissue-engineered blood vessel, the Human Acellular Vessel (HAV), currently being studied in adults suffering from vascular trauma, peripheral arterial disease, and renal failure requiring hemodialysis. In addition to restoring blood flow and providing arteriovenous access in these patients, the HAV has demonstrated the capacity for host cellular remodeling that transformed it into a native-like living tissue. Here the HAV production platform was modified to generate small diameter (3.5mm) vessels for preclinical evaluation. BTTs were placed from the right subclavian artery to the pulmonary artery in juvenile rhesus macaques. Post-operative imaging from 1 week to 6 months using angiography and MRI was used to confirm HAV patency, structure, and quantify blood flow. At explantation, the HAV and surrounding tissues were collected and processed for histological analyses. Results confirmed the feasibility of using the HAV BTTs, but also showed that all macaques had some immunological reactivity to the HAV human extracellular matrix in this xenogeneic animal model. Nonetheless, the HAV BTTs remained patent and performed well for up to six months in animals that had only mild host reactivity. HAV repopulation by host cells expressing smooth muscle and endothelial markers as well as the formation of neoadventitial tissue was also observed. These findings may support use of the HAV as a BTTs in CCHD and potentially other pediatric indications.