The inflammatory response to hypoxic tissue engineered modules

Abstract

Event Abstract Back to Event The inflammatory response to hypoxic tissue engineered modules Nicholas Cober1, 2* and Michael V. Sefton1, 2* 1 University of Toronto, Chemical Engineering and Applied Chemistry, Canada 2 University of Toronto, Institute of Biomaterials and Biomedical Engineering, Canada Tissue modules composed of collagen, endothelial cells (EC), and adipose derived mesenchymal stem cells (adMSC) self-organize upon implantation to create a vascular network [1],[2]. Hypoxia and inflammatory cell infiltration, specifically macrophages, are important aspects of vessel formation and more broadly tissue repair [3],[4]. In order to improve tissue vascularization the interactions between supporting cells (adMSC), host macrophages, and hypoxia during vascularization must be better understood. To this end, we investigated the effect of a 10x increase in adMSC density (to increase oxygen demand) on the host’s inflammatory cell response and the associated impact on tissue vascularization. Normal (1 x 106 cells/mL of collagen preshrinkage) and high (10x) adMSC density modules (0.01 mL) were implanted subcutaneously in SCID/bg mice. The modular tissue implant was explanted and assessed by histology for vessel development and flow cytometry for inflammatory cell infiltration and phenotype at days 1 to 14. Increased adMSC densities lead to augmented host vessel formation but with fewer graft-derived (UEA-1+) vessels compared to standard density controls. We found that the adMSC density did not impact the recruitment of inflammatory cells to the implant site, and only small shifts in macrophage polarization were observed. The combination of increased hypoxic stress and increased growth factor secretion due to a higher adMSC density led to increased host vessel formation. We believe the graft derived EC were being affected detrimentally by increased hypoxic stress and not changes in inflammatory cell infiltration. Further optimization of adMSC density could produce a rapidly vascularizing tissue with improved graft cell survival. Canadian Institute of Health Research; Ontario Graduate Scholarship