Cell surface engineering of the endothelial glycocalyx for prevention of transplant rejection
The endothelial glyxocalyx is a glycoprotein-rich coating on the luminal surface of vascular endothelial cells that has important immune modulatory properties. It is particularly susceptible to injury during organ procurement and this may play a role in triggering early graft inflammation and rejection. Rebuilding the endothelial glycocalyx by enzymatic conjugation of linear polyglycerol polymers containing the bioactive sugar sialic acid onto the surface of human endothelial cells reduced leukocyte binding and inhibited leukocyte-mediated cytotoxicity of endothelial cells. Application of this technology to artery grafts in a mouse model led to substantial reductions in early inflammation, and acute and chronic rejection. Also, this cell surface engineering of vascular endothelial cells in mouse kidney transplant models reduced ischemia-mediated kidney graft failure and allograft rejection. This work provides a foundation for the development a novel cell surface engineering protocol that can be applied to donor organs at the time of procurement and protects them from rejection.