Chimeric Vessel Tissue Engineering Driven by Endothelialized Modules in Immunosuppressed Sprague-Dawley Rats

Abstract

Modular tissue engineering is a means of building functional, vascularized tissues using small (∼1 mm long×0.5 mm diameter) components. While this approach is being explored for its utility in adipose and cardiac tissue engineering and in islet transplantation, the initial question in this study was to assess the fate of the endothelial cells (EC) after transplantation delivered on the surface of modules, without an embedded cell. Rat aortic EC-covered collagen gel modules were transplanted into the omental pouch of allogeneic (outbred) Sprague-Dawley rats with and without immunosuppressive drug treatment (atorvastatin and tacrolimus) for 3-60 days. There was a significant increase in vessel density at all time points in the drug treated rats as compared to untreated rats. Green fluorescent protein (GFP)-positive donor rat aortic EC migrated from the surface of the modules and formed primitive vessels by day 7. In the untreated rats, the GFP-positive cells were not seen after day 7. In drug-treated rats, GFP-positive vessels matured over time, accumulated erythrocytes, were supported by host smooth muscle cells, and formed chimeric vessels that survived until day 60. This resulted in the formation of a densely vascularized, perfusable network by day 60. To our knowledge, this is the first study that demonstrates that primary unmodified EC, without the addition of supporting cells, form a chimeric and stable vascular bed in allogeneic, although drug-treated, animals.