Human blood preconditioned porcine arteries as potential conduits for human transplantation: Proof of concept in rabbit.

Abstract

Tissue-engineered arteries using natural scaffolds could overcome the drawbacks of autografts or artificial conduits used in the repair of many congenital cardiac defects and coronary artery bypass grafts. In this study, we present a novel approach based on the use of decellularized xenogeneic matrix scaffolds preconditioned with human peripheral blood stem cells for future cardiovascular therapy. Cellular components of porcine carotid arteries (n = 40) were removed with physical, chemical and enzymatic means. The decellularized arteries were preconditioned by perfusion with human peripheral blood solution for 10 days. The decellularized and preconditioned grafts were characterized for their histological and functional integrity. To demonstrate proof-of-concept, we used a sub-acute (96 h) rabbit model where either only decellularized porcine arteries or preconditioned with autologous rabbit blood solution were implanted in the abdominal aorta of the animals. The rabbits were examined by Doppler ultrasound and histology. Histology and molecular analysis showed absence of cells and preservation of extracellular cell matrix (ECM) proteins in decellularized porcine arteries. Preconditioning of arteries with human blood showed a thin lining of intima with blood and cells. In the rabbit implant model, although blood flow was detected in all rabbits at 24 h, the animals implanted with only decellularized arteries showed lumen filled with thrombus. However, in preconditioned arteries, thrombosis was not seen at either 24 or 96 h. Taken together, these results suggest that these decellularization and preconditioning protocols using autologous blood may be adaptable for successful tissue-engineering of xeno-arteries for human application. However, further research to improve preconditioning efficiency and long-term animal studies are needed.