E12

Long-term protection from human complement-dependent damage could be achieved through genetic expression of human RCA molecules in xenogeneic cells. Toward this end, experiments have been conducted with xenogeneic cell types that were transfected with cDNA for various human RCA molecules, resulting in expression of these proteins on cell membranes and protection from human complement. These findings served as the basis for several groups to develop animals transgenic for human RCA molecules. Cells and organs from transgenic mice expressing different human RCA are protected from the effects of xenoactive antibody and complement. Similarly, transgenic swine expressing different human RCA show resistance to hyperacute rejection in both ex vivo and in vivo models. Although transgenic porcine organs have been shownrepeatly to avoid HAR in nonhuman primates, these grafts are lost through a process of acute vascular xenograft rejection.

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