The innate immune system contributes to tissue-engineered vascular graft performance

The first clinical trial of tissue-engineered vascular grafts (TEVGs) identified stenosis as the primary cause of graft failure. In this study, we aimed to elucidate the role of the host immune response in the development of stenosis using a murine model of TEVG implantation. We found that the C.B-17 wild-type (WT)mouse (control) undergoes a dramatic stenotic response, which is nearly completely abolished in the immunodeficient SCID/ beige (bg) variant. SCID mice, which lack an adaptive im- mune systemdue to the absence of T and B lymphocytes, experienced rates of stenosis comparable to WT controls (average luminal diameter,WT: 0.07160.035 mm, SCID: 0.13760.032mm,SCID/bg:0.80460.039mm;P<0.001). The bg mutation is characterized byNK cell and platelet dysfunction, and systemic treatment of WT mice with either NK cell–neutralizing (anti–NK 1.1 antibody) or antiplatelet (aspirin/Plavix [clopidogrel bisulfate]; Asp/ Pla) therapy achieved nearly half the patency observed in the SCID/bg mouse (NK Ab: 0.35660.151mm, Asp/Pla: 0.452 6 0.130 mm). Scaffold implantation elicited a blunted immune response in SCID/bg mice, as dem- onstrated by macrophage number andmRNAexpression of proinflammatory cytokines in TEVG explants. Impli- cating the initial innate immune response as a critical factor in graft stenosis may provide a strategy for prog- nosis andtherapy of second-generationTEVGs.—Hibino, N.,Mejias, D.,Pietris,N.,Dean, E.,Yi, T.,Best,C.,Shinoka, T., Breuer, C. The innate immune system contributes to tissue-engineered vascular graft performance.