Fate of Endothelialized Modular Constructs Implanted in an Omental Pouch in Nude Rats

Abstract

Modular tissue engineering is a novel microscale approach that aims to assemble tissue constructs with inherent vascularization. We transplanted endothelialized modules (sub-millimeter-sized collagen gel cylinders covered with human umbilical vein endothelial cell [HUVEC] on the outside surface) in the omental pouch of nude rats to characterize remodeling of the collagen gels and the fate of the transplanted HUVEC. Endothelialized modules randomly assembled in vivo to form channels among individual modules that persisted for at least 14 days. Transplanted HUVEC migrated and formed primitive vessels in these channels; however, host inflammation limited HUVEC survival beyond 3 days. Temporary depletion of peritoneal macrophages (by treatment with clodronate liposomes) prolonged the survival of HUVEC-derived vessels to 7 days, and some vessels appeared to be perfused with host erythrocytes and invested with host vascular cells (either rat von Willebrand factor or smooth muscle alpha-actin-positive cells). Despite treatment, HUVEC were presumed to be still subject to immune rejection. The presence of primitive HUVEC-derived vessels is encouraging in this first in vivo study of the modular approach, in a partially immune-compromised animal model. It suggests that with appropriate attention to the host response to transplanted endothelial cells and improved vessel survival, cells that would be embedded in modules could be adequately perfused.