EFFECTS OF GRAFT POOLING OF FETAL-RAT AND MOUSE-TISSUE AND IMMUNOSUPPRESSION IN THE 6-HYDROXYDOPAMINE RAT MODEL OF PARKINSONS-DISEASE

We employed intracerebral co-transplantation of foetal xenogeneic stri atal mouse tissue and allogeneic rat substantia nigra into the adult r at brain to elucidate the effects of xenogeneic mouse graft on the fun ction and survival of an allogeneic rat graft in 6-hydroxydopamine les ioned Sprague-Dawley rats. Foetal mouse striatum (STR) and rat substan tia nigra (VM) were transplanted as non-pooled separate deposits or a pooled cell suspension with or without cyclosporin A (Cy A). Immunosup pressed recipients of pooled rat and mouse co-grafts showed a signific antly better compensation of amphetamine-induced rotational behaviour compared with nonimmunosuppressed animals with pooled rat and mouse co -grafts 3 and 6 weeks post-grafting. Tyrosine hydroxylase (TH) immunoh istochemistry revealed a non-significant reduction in survival in pool ed (1805.3+/-367.5 cells) rat and mouse co-transplants without immunos uppression compared with immunosuppressed pooled (3383.3+/-732.7 cells ) animals with allo- and xenogeneic tissue and controls (3506.4+/-839. 3 cells). Graft volumes were significantly reduced in pooled transplan ts without immunosuppression (0.1+/-0.026 mm(3); ANOVA post-hoc Scheff e F-test, P<0.0001) compared with immunosuppressed recipients (0.7+/-0 .1 mm(3)) and controls (0.6+/-0.1 mm(3)). In non pooled allo- and xeno geneic grafts without immunosuppression the survival rate of the TH-im munoreactive cells and graft volumes were reduced (2359.3+/-479.5 cell s; 0.2+/-0.043 mm(3)) compared with immunosuppressed animals (2927.3+/ -946.6 cells; 0.6+/-0.2 mm(3)) and controls (2701.1+/-693.8 cells; 0.3 +/-0.1 mm(3)) without reaching a level of significance. Rejection of m ouse tissue was observed in all non-immunosuppressed recipients. In su mmary: (i) continued immunosuppression yielded significant beneficial effects on function and beneficial effects on survival of pooled graft s with an immunogenetic disparity; (ii) the rejection of a xenogeneic graft component may compromise survival and function of other, allogen eic graft components; and (iii) transplantation of no-pooled allo- and xenogeneic tissues may result in a better survival of the graft compa red with pooled cell suspensions.