Simultaneous Transplantation of Fetal Ventral Mesencephalic Tissue and Encapsulated Genetically Modified Cells Releasing GDNF in a Hemi-Parkinsonian Rat Model of Parkinson’s Disease

Alberto Perez-Bouza, Stefano Di Santo, Stefanie Seiler, Morten Meyer, Lukas Andereggen, Alexander Huber, Raphael Guzman, Hans R. Widmer

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Abstrakt

Transplantation of fetal ventral mesencephalic (VM) neurons for Parkinson's disease (PD) is limited by poor survival and suboptimal integration of grafted tissue into the host brain. In a 6-OHDA rat model of PD we investigated the feasibility of simultaneous transplantation of rat fetal VM tissue and polymer-encapsulated C2C12 myoblasts genetically modified to produce glial cell line-derived neurotrophic factor or mocktransfected myoblasts on graft function. Amphetamine-induced rotations were assessed prior and 2, 4, 6 and 9 weeks post-transplantation. We found that rats grafted with VM transplants and GDNF-capsules showed a significant functional recovery already 4 weeks after implantation. In contrast, rats from the VM transplant and mock-capsule group did not improve at any time point analyzed. Moreover, we detected a significantly higher number of tyrosine hydroxylase-immunoreactive (TH-ir) cells per graft (2 fold), a tendency for a larger graft volume and an overall higher TH-ir fiber outgrowth into the host brain (1.7 fold) in the group with VM transplants and GDNF-capsules as compared to the VM transplant and mock-capsule group. Most prominent was the TH-ir fiber outgrowth towards the capsule (9 fold). Grafting of GDNF pre-treated VM transplants in combination with the implantation of GDNF-capsules resulted in a tendency for a higher TH-ir fiber outgrowth into the host brain (1.7 fold) as compared to the group transplanted with untreated VM transplants and GDNF-capsules. No differences between groups were observed for the number of surviving TH-ir neurons or graft volume. In conclusion, our findings demonstrate that simultaneous transplantation of fetal VM tissue and encapsulated GDNF-releasing cells is feasible and support the graft survival and function. Pre-treatment of donor tissue with GDNF may offer a way to further improve cell transplantation approaches for PD.

OriginalsprogEngelsk
TidsskriftCell Transplantation
Vol/bind26
Udgave nummer9
Sider (fra-til)1572-1581
ISSN0963-6897
DOI
StatusUdgivet - 2017

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