gms | German Medical Science

Objective: The principal goal of neuroregenerative therapies in neurodegenerative diseases is to restore the anatomy and the function of damaged neural circuits. While stem cell transplantation is considered to be a promising therapeutic approach, knowing the fate of transplanted cells using appropriate markers is essential. In our study we investigate the potential of GFP transgenic rats as future cell source for monitoring the cellular fate of transplanted cells during migration and differentiation phases in vivo.

Methods: The most common rat model of Parkinson’s disease (PD) is based on unilateral injections of 6-hydroxydopamine into the medial forebrain bundle resulting in a complete loss of dopaminergic (DAergic) nigral neurons and leading to a complete depletion of dopamine within the striatum. Dissociated ventral mesencephali of E14 (CRL=10-11mm) GFP Lewis rats were transplanted into the striatum of hemiparkinsonian Sprague Dawley rats. In vew of the fact that the donor and the recipient belonged to two different rat strains, special focus was set on the graft survival, expression of GFP in the host brain and how the graft survival correlated with the immunosuppression. Transplanted animals were divided into two groups (n=20), one with and one without immunosuppression. Half of the animals of each group were sacrificed after two weeks after transplantation (short-term cell survival) and the other half after four weeks (long-term cell survival). Lesion and transplantation effects were evaluated with apomorphine- and amphetamine-induced rotations six weeks after lesion and and four weeks after transplantation. Survival and integration of DAergic and GFP neurons were assessed by immunohistochemical analyses.

Results: All experimental groups showed a significant compensation after transplantation in drug-induced rotations. There was no difference in drug-induced rotations between the immunosuppressed and the non-immunosuppressed animals both in short-term and long-term cell survival groups. Morphological analysis revealed that the fact that donor and recipient belonged to two different rat strains, did not play a role in graft survival, since immunosuppression did not improve survival patterns. In addition, GFP expression remained stable in short-term as well as in long-term cell survival groups with or without immunosuppression.

Conclusions: In summary GFP rats serve as an excellent tool to study neural stem cell plasticity in the neurotransplantation paradigm and to promote graft survival and integration as well as graft-host-interactions in a rat model of PD.