Fate of αGal +/+ pancreatic islet grafts after transplantation into αGal knockout mice

  Background:  Important phylogenetic differences between pig and human tissues prevent xenotransplantation from becoming a clinically feasible option. Humans lack the galactose‐ α 1,3‐galactose ( α Gal) epitope on endothelial cell surfaces and therefore have preformed anti‐ α Gal antibodies. The role of these antibodies in rejection of non‐vascular xenografts remains controversial. This study investigared the role of anti‐ α Gal antibodies in rejection of non‐vascularized α Gal+/+ grafts in α Gal −/− mice. Methods:  α Gal +/+ and α Gal −/− pancreatic islets were transplanted under the renal capsule of streptozotocin‐induced diabetic (1) α Gal −/− mice and (2) α Gal +/+ mice. α Gal −/− recepients were immunized with rabbit red blood cell membranes (RRBCs) to produce elevated anti‐ α Gal antibody levels. Results:  Six of the 18 α Gal −/− mice rejected the α Gal +/+ grafts within 68 days whereas indefinite graft survival was achieved in the control groups. Animals with surviving islet grafts were challenged with α Gal +/+ skin grafts. Although all α Gal +/+ skin grafts were rejected within 58 days, the islet grafts remained intact. This observation correlated with the level of α Gal expression (which was very low on islets compared to skin) rather than the actual titre of anti‐ α Gal antibody. Discussion:  The results suggest that the level of α Gal expression plays an important role in graft survival. Therefore, its removal is important in the development of a pig islet donor for future clinical therapy.