Porcine neural xenografts: what are the issues?

The allografting of embryonic neural tissue into the CNS of animals with experimental lesions and patients with neurodegenerativc conditions has shown that this tissue survives, makes and receives synapses, and ameliorates behavioural deficits without inducing a significant rejection process. There are though, major problems with the use of aborted human tissue in clinical programmes of transplantation which has lead to the search for alternative sources of cells, including embryonic porcine tissue. However there are two major issues relating to the use of this tissue: (a) the risk of zoonotic infection especially with porcine endogenous retroviruses (PERVs); and (b) the loss of the tissue to an immunologically based rejection process, and it is this latter issue that forms the basis of this chapter. The rejection of neural xenografts has clearly been shown to involve T cell-directed processes although there is now increasing evidence that complement and humoral immune mediators may also play a role. This suggests that transgenic pigs expressing regulators of the human complement cascade may offer an advantage over normal porcine tissue in any clinical neural xenograft programmes. However the extent to which these different immune processes are interdependent, and the contribution of each of them to the actual loss of the grafted tissue is currently unresolved.