Schwarz S C, Sauer H, Oertel W H, Earl C D, Kupsch A R
Klinikum Grosshadern, Department of Neurology, Munich, Germany.
Exp Brain Res. 1997 Jun;115(1):71-82. doi: 10.1007/pl00005687.
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.
我们将胎鼠异种纹状体组织和同种异体大鼠黑质共同移植到成年大鼠脑内，以阐明异种小鼠移植物对6-羟基多巴胺损伤的斯普拉格-道利大鼠中同种异体大鼠移植物的功能和存活的影响。胎鼠纹状体（STR）和大鼠黑质（VM）作为未混合的单独移植物或混合细胞悬液进行移植，同时使用或不使用环孢素A（Cy A）。与移植后3周和6周未免疫抑制的混合大鼠和小鼠共同移植物的动物相比，免疫抑制的混合大鼠和小鼠共同移植物的接受者对苯丙胺诱导的旋转行为的补偿明显更好。酪氨酸羟化酶（TH）免疫组织化学显示，未免疫抑制的混合（1806.3±367.5个细胞）大鼠和小鼠共同移植中，与免疫抑制的混合（3383.3±732.7个细胞）的同种异体和异种组织动物及对照组（3506.4±839.3个细胞）相比，存活率无显著降低。与免疫抑制的接受者（0.7±0.1 mm³）和对照组（0.6±0.1 mm³）相比，未免疫抑制的混合移植中移植物体积显著减小（0.1±0.026 mm³；方差分析事后Scheffe F检验，P<0.0001）。在未免疫抑制的非混合同种异体和异种移植物中，TH免疫反应性细胞的存活率和移植物体积与免疫抑制的动物（2927.3±946.6个细胞；0.6±0.2 mm³）和对照组（2701.1±693.8个细胞；0.3±0.1 mm³）相比降低（2359.3±479.5个细胞；0.2±0.043 mm³），但未达到显著水平。在所有未免疫抑制的接受者中均观察到小鼠组织的排斥反应。总之：（i）持续免疫抑制对具有免疫遗传差异的混合移植物的功能和存活产生显著有益影响；（ii）异种移植物成分的排斥可能损害其他同种异体移植物成分的存活和功能；（iii）与混合细胞悬液相比，非混合同种异体和异种组织的移植可能导致移植物更好的存活。
