gms | German Medical Science

Objective: Stem cell transplantation is considered to be a promising therapeutic approach for neurodegenerative diseases. In animal models, appropriate labelled donor cells are essential in order to study differentiation and integration of grafted cells. GFP transgenic rats (Inoue et al, 2005) express GFP ubiquitously and provide a promising donor source. In our study, GFP cells were transplanted in a rat model of Parkinson Disease (PD) and GFP expression was evaluated after transplantation.

Methods: A rat model of PD is based on unilateral injections of 6-hydroxydopamine into the medial forebrain bundle, resulting in a complete loss of dopaminergic (DA) neurons and leading to a depletion of DA within the relevant striatum. In this study, cell suspensions rich in DA neurons derived from dissociated ventral mesencephala of E14 (CRL = 10-11 mm) GFP Lewis rats were transplanted into the lesioned striatum of PD Sprague Dawley rats. Intrastriatal grafts of DA neural progenitor cells can reinnervate the striatum and restore, at least partly, lesion-induced behavioural deficits. Concerning the fact that donor and recipient belong to two different rat strains, transplanted animals were divided into two groups, one with and one without immunosuppression. Lesion and transplantation effects were evaluated with drug-induced rotations 6 weeks after lesion and 2, 4, 10 and 15 weeks after transplantation. Animals of each group were sacrificed 2, 4, 10 and 15 weeks after transplantation and brains were analysed by immunohistochemistry and stereology.

Results: Grafted cells survived and integrated successfully in the host since all grafted groups showed a significant compensation (p<0.05) in apomorphin- and amphetamine-induced rotations compared to lesion controls. There was no significant difference between immunosuppressed and non-immunosuppressed animals in rotation behaviour, number of surviving cells, graft volume or fibre density showing that graft survival does not correlate with immunosuppression. In addition, GFP expression remained stable in 80.0% of all tyrosine hydroxylase positive cells proving that GFP rats are an excellent donor source for transplantation.

Conclusions: The fact that donor and recipient belonged to two different rat strains played no role in graft survival. Since immunosuppression did not influence graft survival, it will not be necessary in coming studies. Furthermore, GFP expression remained stable, which indicates that GFP rats serve as an excellent tool for studying neural stem plasticity in the transplantation paradigm for neurodegenerative diseases.