Simultaneous Transplantation of Fetal Ventral Mesencephalic Tissue and Encapsulated Genetically Modified Cells Releasing GDNF in a Hemi-Parkinsonian Rat Model of Parkinson’s Disease
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-hydroxydopamine rat model of PD, we investigated the feasibility of simultaneous transplantation of rat fetal...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-09-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/0963689717721202 |
| _version_ | 1819297865123495936 |
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| author | Alberto Perez-Bouza Stefano Di Santo Stefanie Seiler Morten Meyer Lukas Andereggen Alexander Huber Raphael Guzman Hans R. Widmer PhD |
| author_facet | Alberto Perez-Bouza Stefano Di Santo Stefanie Seiler Morten Meyer Lukas Andereggen Alexander Huber Raphael Guzman Hans R. Widmer PhD |
| author_sort | Alberto Perez-Bouza |
| collection | DOAJ |
| description | 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-hydroxydopamine 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 (GDNF) or mock-transfected myoblasts on graft function. Amphetamine-induced rotations were assessed prior to transplantation and 2, 4, 6 and 9 wk posttransplantation. We found that rats grafted with VM transplants and GDNF capsules showed a significant functional recovery 4 wk 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 toward the capsule (9-fold). Grafting of GDNF-pretreated 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. Pretreatment of donor tissue with GDNF may offer a way to further improve cell transplantation approaches for PD. |
| first_indexed | 2024-12-24T05:20:47Z |
| format | Article |
| id | doaj.art-614d04c992a84acbb328745d8bb08b1a |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-24T05:20:47Z |
| publishDate | 2017-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-614d04c992a84acbb328745d8bb08b1a2022-12-21T17:13:28ZengSAGE PublishingCell Transplantation0963-68971555-38922017-09-012610.1177/0963689717721202Simultaneous Transplantation of Fetal Ventral Mesencephalic Tissue and Encapsulated Genetically Modified Cells Releasing GDNF in a Hemi-Parkinsonian Rat Model of Parkinson’s DiseaseAlberto Perez-Bouza0Stefano Di Santo1Stefanie Seiler2Morten Meyer3Lukas Andereggen4Alexander Huber5Raphael Guzman6Hans R. Widmer PhD7 Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster, Bern University Hospital, University of Bern, Bern, Switzerland Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster, Bern University Hospital, University of Bern, Bern, Switzerland Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster, Bern University Hospital, University of Bern, Bern, Switzerland Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster, Bern University Hospital, University of Bern, Bern, Switzerland Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster, Bern University Hospital, University of Bern, Bern, Switzerland Present address: Departments of Neurosurgery and Biomedicine, University Hospital of Basel, Basel, Switzerland Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster, Bern University Hospital, University of Bern, Bern, SwitzerlandTransplantation 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-hydroxydopamine 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 (GDNF) or mock-transfected myoblasts on graft function. Amphetamine-induced rotations were assessed prior to transplantation and 2, 4, 6 and 9 wk posttransplantation. We found that rats grafted with VM transplants and GDNF capsules showed a significant functional recovery 4 wk 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 toward the capsule (9-fold). Grafting of GDNF-pretreated 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. Pretreatment of donor tissue with GDNF may offer a way to further improve cell transplantation approaches for PD.https://doi.org/10.1177/0963689717721202 |
| spellingShingle | Alberto Perez-Bouza Stefano Di Santo Stefanie Seiler Morten Meyer Lukas Andereggen Alexander Huber Raphael Guzman Hans R. Widmer PhD Simultaneous Transplantation of Fetal Ventral Mesencephalic Tissue and Encapsulated Genetically Modified Cells Releasing GDNF in a Hemi-Parkinsonian Rat Model of Parkinson’s Disease Cell Transplantation |
| title | Simultaneous Transplantation of Fetal Ventral Mesencephalic Tissue and Encapsulated Genetically Modified Cells Releasing GDNF in a Hemi-Parkinsonian Rat Model of Parkinson’s Disease |
| title_full | Simultaneous Transplantation of Fetal Ventral Mesencephalic Tissue and Encapsulated Genetically Modified Cells Releasing GDNF in a Hemi-Parkinsonian Rat Model of Parkinson’s Disease |
| title_fullStr | Simultaneous Transplantation of Fetal Ventral Mesencephalic Tissue and Encapsulated Genetically Modified Cells Releasing GDNF in a Hemi-Parkinsonian Rat Model of Parkinson’s Disease |
| title_full_unstemmed | Simultaneous Transplantation of Fetal Ventral Mesencephalic Tissue and Encapsulated Genetically Modified Cells Releasing GDNF in a Hemi-Parkinsonian Rat Model of Parkinson’s Disease |
| title_short | Simultaneous Transplantation of Fetal Ventral Mesencephalic Tissue and Encapsulated Genetically Modified Cells Releasing GDNF in a Hemi-Parkinsonian Rat Model of Parkinson’s Disease |
| title_sort | simultaneous transplantation of fetal ventral mesencephalic tissue and encapsulated genetically modified cells releasing gdnf in a hemi parkinsonian rat model of parkinson s disease |
| url | https://doi.org/10.1177/0963689717721202 |
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