Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity

Disruption of the thrombospondin 2 gene (Thbs2) in mice results in a comple x phenotype characterized chiefly by abnormalities in fibroblasts, connecti ve tissues, and blood vessels. Consideration of this phenotype suggested to us that the foreign body reaction (FBR) might be altered in thrombospondin 2 (TSP2)-null mice. To investigate the participation of TSP2 in the FBR, p olydimethylsiloxane (PDMS) and oxidized PDMS (ox-PDMS) disks were implanted in TSP2-null and control mice. Growth of TSP2-null and control skin fibrob lasts in vitro also was evaluated on both types of disks. Normal fibroblast s grew as a monolayer on both surfaces, but attachment of the cells to ox-P DMS was weak and sensitive to movement. TSP2-null fibroblasts grew as aggre gates on both surfaces, and their attachment was further compromised on ox- PDMS. After a 4-week implantation period, both types of PDMS elicited a sim ilar FBR with a collagenous capsule in both TSP2-null and control mice, How ever, strikingly, the collagenous capsule that formed in TSP2-null mice was highly vascularized and thicker than that formed in normal mice. In additi on, abnormally shaped collagen fibers were observed in capsules from mutant mice. These observations indicate that the presence or absence of an extra cellular matrix component, TSP2, can influence the nature of the FBR, in pa rticular its vascularity. The expression of TSP2 therefore could represent a molecular target for local inhibitory measures when vascularization of th e tissue surrounding an implanted device is desired.