Traditional tissue engineering methods have led to the construction of blood vessel grafts by seeding biodegradable scaffolds with cells isolated from adult tissues. As the new tissue grows, the scaffold degrades, leaving a purely biological graft. Pre-clinical studies have shown that the primary mode of failure in these grafts is stenosis (narrowing of the internal opening of the vessel). It seems that even though the cells are supplied with the necessary biological and physical stimuli to coax them towards vascular formation ex vivo, these conduits lack the multitude of cues present in the in vivo environment to prevent graft failure. Therefore, a better technology is needed to enable rational design of durable engineered vascular tissues to be used in the clinical setting.
Our strategy to engineer vascular tissues is to recapitulate blood vessel formation as it occurs during embryonic development. Baboon stem cells are optimally suited for engineering vascular tissues. These stem cells can give rise to unlimited numbers of specialized cells organized according to the native architecture of blood vessels. Our previous work has demonstrated the potential of baboon embryonic stem cells to differentiate into endothelial and smooth muscle cells, the key cellular components in blood vessels. The goal of this study is to establish the feasibility of engineering these cells into fully viable, 2-3 cm in length, 3-4 mm in diameter, vascular tissues, and to implant an engineered blood vessel into a baboon to evaluate its short-term therapeutic values and capacity to remain fully open (this capacity is known as patency).
