Effects of graft pooling of foetal rat and mouse tissue and immunosuppression in the 6-hydroxydopamine rat model of Parkinson’s disease |
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| Authors: | Sigrid C Schwarz Hansjörg Sauer Wolfgang H Oertel Christopher D Earl Andreas R Kupsch |
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| Institution: | (1) Klinikum Grosshadern, Department of Neurology, Marchioninistrasse 15, D-81377 Munich, Germany, DE;(2) University of Lund, Department of Medical Cell Research, Biskopsgatan 5, S-22362 Lund, Sweden, SE;(3) University of Ulm, Department of Neurology (RKU), Oberer Eselsberg 45, D-89081 Ulm, Germany; Tel.: +49 731 1771207, DE |
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| 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 SchefféF-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.
Received: 25 March 1996 / Accepted: 1 December 1996 |
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| Keywords: | Brain Co-transplantation 6-hydroxydopamine Tyrosinehydroxylase Immunosuppression |
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