Effects of graft pooling of foetal rat and mouse tissue and immunosuppression in the 6-hydroxydopamine rat model of Parkinson's disease

Abstract

We employed intracerebral co-transplantation of foetal xenogeneic striatal mouse tissue and allogeneic rat substantia nigra into the adult rat brain to elucidate the effects of xenogeneic mouse graft on the function and survival of an allogeneic rat graft in 6-hydroxydopamine lesioned Sprague-Dawley rats. Foetal mouse striatum (STR) and rat substantia nigra (VM) were transplanted as non-pooled separate deposits or a pooled cell suspension with or without cyclosporin A (Cy A). Immunosuppressed recipients of pooled rat and mouse co-grafts showed a significantly better compensation of amphetamine-induced rotational behaviour compared with non-immunosuppressed animals with pooled rat and mouse co-grafts 3 and 6 weeks post-grafting. Tyrosine hydroxylase (TH) immunohistochemistry revealed a non-significant reduction in survival in pooled (1806.3+/-367.5 cells) rat and mouse co-transplants without immunosuppression 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 transplants without immunosuppression (0.1+/-0.026 mm3; ANOVA post-hoc Scheffe F-test, P<0.0001) compared with immunosuppressed recipients (0.7+/-0.1 mm3) and controls (0.6+/-0.1 mm3). In non-pooled allo- and xenogeneic grafts without immunosuppression the survival rate of the TH-immunoreactive cells and graft volumes were reduced (2359.3+/-479.5 cells; 0.2+/-0.043 mm3) compared with immunosuppressed animals (2927.3+/-946.6 cells; 0.6+/-0.2 mm3) and controls (2701.1+/-693.8 cells; 0.3+/-0.1 mm3) without reaching a level of significance. Rejection of mouse tissue was observed in all non-immunosuppressed recipients. In summary: (i) continued immunosuppression yielded significant beneficial effects on function and beneficial effects on survival of pooled grafts with an immunogenetic disparity; (ii) the rejection of a xenogeneic graft component may compromise survival and function of other, allogeneic graft components; and (iii) transplantation of non-pooled allo- and xenogeneic tissues may result in a better survival of the graft compared with pooled cell suspensions.