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

Autor: Chandra, Abhilash P., Salvaris, Evelyn, Walters, Stacey N., Murray-Segal, Lisa, Gock, Hilton, Lehnert, Anne M., Wong, Jeffrey K. W., Cowan, Peter J., d'Apice, Anthony J. F., O'Connell, Philip J.
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Zdroj: Xenotransplantation; Jul2004, Vol. 11 Issue 4, p323-331, 9p
Abstrakt: Important phylogenetic differences between pig and human tissues prevent xenotransplantation from becoming a clinically feasible option. Humans lack the galactose-α1,3-galactose (αGal) epitope on endothelial cell surfaces and therefore have preformed anti-αGal antibodies. The role of these antibodies in rejection of non-vascular xenografts remains controversial. This study investigared the role of anti-αGal antibodies in rejection of non-vascularized αGal+/+ grafts in αGal -/- mice. αGal +/+ and αGal -/- pancreatic islets were transplanted under the renal capsule of streptozotocin-induced diabetic (1) αGal -/- mice and (2) αGal +/+ mice. αGal -/- recepients were immunized with rabbit red blood cell membranes (RRBCs) to produce elevated anti-αGal antibody levels. Six of the 18 αGal -/- mice rejected the αGal +/+ grafts within 68 days whereas indefinite graft survival was achieved in the control groups. Animals with surviving islet grafts were challenged with αGal +/+ skin grafts. Although all αGal +/+ skin grafts were rejected within 58 days, the islet grafts remained intact. This observation correlated with the level of αGal expression (which was very low on islets compared to skin) rather than the actual titre of anti-αGal antibody. The results suggest that the level of αGal 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index