gms | German Medical Science

Objective: Regenerative therapy in patients with Parkinson’s disease (PD) by transplantation of ventral mesencephalic (VM) dopaminergic grafts is a highly promising prospect for future clinical treatment.

The aim of this study was to compare different transplantation strategies and grafting locations. Functional recovery and graft survival of human-derived VM grafts were evaluated after transplantation into the nigra or the striatum in a rat model of PD; the use of single cell suspensions or tissue pieces, and glass capillary or metal cannula were compared.

Methods: In a rat model of PD unilateral injections of 6-OHDA into the medial forebrain bundle (MFB) lead to a depletion of dopamine (DA) within the relevant striatum. 4 weeks after the lesion, fetal (6–12 weeks) human VM cell suspensions were transplanted using different techniques and different target locations: groups 1 and 2 received a single cell suspension transplanted via glass capillary into the nigra and into the striatum respectively by dividing one VM in two. Groups 3 and 4 were transplanted by metal cannula into the striatum and received small tissue pieces and single cell suspension respectively by dividing the VM. Each animal received a total of 4x10⁵ cells. Drug-induced rotation tests were performed 3, 6, 10, and 14 weeks after transplantation. Immunosuppression was effected by daily injections of cyclosporine.

Results: All groups transplanted into the striatum showed a significant reduction in the amphetamine-induced rotation test after 10 and 14 weeks, whereas no changes were seen in group 1. Groups 1, 2, and 3 showed a significant reduction in the apomorphine-induced rotation test after 6 weeks, whereas group 4 only showed a tendency towards reduction.

The survival of TH⁺ cells was highest in groups 1 and 3 with a mean of 1100 cells. In groups 2 and 4, 600 and 800 cells survived, respectively.

Conclusions: Human VM cells transplanted into the 6-OHDA rat model survived well for up to 14 weeks. The reduction in the amphetamine-induced rotation tests in all groups transplanted into the striatum demonstrates a functional recovery, whereas human grafts in the nigra do not seem to increase the disposable dopamine in the striatum. The transplantation of tissue pieces by metal cannula seems to be more favorable when compared to the transplantation of a single cell suspension by cannula, which is demonstrated by a stronger reduction in the rotation tests and better cell survival. Taken together, our study provides useful and important information for further methodological refinements of neural transplantation for PD.