Chronic allograft rejection associated vasculopathy and synthetic biodegradable vascular grafts: a lesson to learn?

In chronic allografts, graft vessels eventually develop so-called "transplant vascular sclerosis" or "intimal hyperplasia". A major question is whether the cells in the neointima are donor or recipient derived. The process of transplant vascular sclerosis closely resembles the remodeling of the vascular wall as seen when synthetic biodegradable small caliber vascular grafts are implanted. In this model, the cells in the newly developing neointima as well as neomedia are, by definition, recipient derived. By using cardiac allografts as well as aortic allografts exchanged between a female donor and a male recipient (rats), the origin of the neointimal vascular smooth muscle cells could be traced by looking for the Y-chromosome in isolated (alpha-actin positive) intimal cells using PCR. In both models these intimal cells were found to be of recipient-origin. It is proposed, that, basically, this remodeling process is part of a normal healing process. Whereas in biodegradable grafts this "healing process" appears to be self limiting, in allografts the process goes on beyond the needs of functional repair, eventually, in some cases, leading to total vascular occlusion. Future therapeutic protocols might try and aim at controlling this essentially normal repair process.