THE IMMUNOGENICITY OF THE EXTRACELLULAR-MATRIX IN ARTERIAL XENOGRAFTS

Background. Determinants of xenograft immunogenicity are poorly charac terized. The showed previously that decellularized arterial xenografts (DAXs) dilate, whereas decellularized arterial isografts (DAls) and a llografts do not, suggesting an interspecies, rather than an intraspec ies, immunogenicity of the arterial extracellular matrix leading to ch ronic rejection. Now we have investigated the immunogenicity of the ar terial extracellular matrix in xenografts and its impact on chronic in jury (elastin lysis) and remodeling (graft dilation). Methods. Diamete r and elastin content were measured in DAls and DAXs from hamster do m t (concordant combination) and guinea pig to rat (discordant combinati ons) at 8 weeks, We also characterized the immune effecters infiltrati ng DAls and DAXs by immunohistochemistry after 6 hours to 4 weeks of i mplantation. Results were compared with nondecellularized isografts an d xenografts. Last, the impact of the donor-recipient phylogenetic dis tance on monocyte-macrophage penetration into the media was assessed i n three xenograft combinations. Results, DAXs from guinea pig, but not from hamster, were aneurysmal at 8 weeks. Elastin lysis paralleled gr aft dilation. DAXs, but not DAls, were infiltrated by monocytes, macro phages, T lymphocytes, and immunoglobulins. The donor-recipient combin ation did not effect the phenotype of the inflammatory infiltrate in D AXs, but it modified the kinetics of monocyte-macrophage penetration i nto the media. The absence of decellularization changed the inflammato ry infiltrate phenotype (absence of macrophages) but had little impact on DAX injury and remodeling. Conclusions, DAX immunogenicity account s for most of chronic arterial xenograft injury which is modulated by the donor-recipient combination. The immunogenicity of arterial xenogr afts, unlike allografts, is supported by the extracellular matrix in a ddition to the cells and could influence the long-term fate of xenogra fts.