The effect of three-dimensional matrix-embedding of endothelial cells on the humoral and cellular immune response

The endothelium is a unique immunologic target. The first host-donor reaction in any cell, tissue or organ transplant occurs at the blood-tissue interface, the endothelium. When endothelial cells are themselves the primary component of the implant a second set of immunologic reactions arises. Injections of free endothelial cell implants elicit a profound major histocompatibility complex (MHC) II dominated immune response with significant sensitivity, cascade enhancement and immune memory. Endothelial cells embedded within three-dimensional matrices retain all the biosecretory capacity of quiescent endothelial cells. Perivascular implants of such cells are the most potent inhibitor of intimal hyperplasia and thrombosis following controlled vascular injury, but without any immune reactivity. Allo- and even xenogeneic endothelial cells evoke no significant humoral or cellular immune response in immunocompetent hosts when embedded within matrices. Moreover, endothelial implants are immunomodulatory, reducing the extent of the memory response to previous free cell implants. Attenuated immunogenicity results in muted activation of adaptive and innate immune cells. These findings point toward a pivotal role of matrix-cell-interconnectivity for the cellular immune phenotype and might therefore assist in the design of extracellular matrix components for successful tissue engineering.