Long-term survival of encapsulated GDNF secreting cells implanted within the striatum of parkinsonized rats
| Autor: | Luisa Ugedo, Laura Grandoso, Gorka Orive, Alicia Rodríguez, Iván Manuel, Mercedes Zumárraga, Isabel Ulibarri, José Ángel Ruiz-Ortega, Gurutz Linazasoro, Aurora Arrúe, Rafael Rodríguez-Puertas, José Luis Pedraz, Rosa Maria Hernandez, Sara Ponce |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Cell Survival Dopamine Drug Compounding Pharmaceutical Science Striatum Neuroprotection Cell Line Levodopa Rats Sprague-Dawley Drug Delivery Systems Neurotrophic factors Internal medicine medicine Glial cell line-derived neurotrophic factor Animals Glial Cell Line-Derived Neurotrophic Factor Behavior Animal Tyrosine hydroxylase biology business.industry Homovanillic Acid Parkinson Disease Anatomy Fibroblasts Corpus Striatum Rats Transplantation Neuroprotective Agents Endocrinology nervous system Cell culture biology.protein 3 4-Dihydroxyphenylacetic Acid business medicine.drug |
| Zdroj: | International Journal of Pharmaceutics. 343:69-78 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2007.05.027 |
| Popis: | Several findings suggest that glial cell line-derived neurotrophic factor (GDNF) may be a useful tool to treat parkinsonism by acting as a neuroprotective and neurotrophic factor for dopaminergic neurotransmission systems. In the present study, we implanted alginate-poly-L-lysine-alginate microcapsules containing immobilized Fischer rat 3T3 fibroblasts transfected to produce GDNF in vitro into the striatum of 6-hydroxydopamine (6-OHDA) lesioned rats. Microencapsulated GDNF secreting cells were stable for at least 3 weeks in vitro. Intrastriatal implantation of microencapsulated GDNF secreting cells into 6-OHDA lesioned rats resulted in a decrease in apomorphine-induced rotations by 84%, 64%, 84%, 60% and 52% (2, 5, 8, 16 and 24 weeks, respectively) with respect to the value before implantation and with respect to the value obtained from the empty microcapsule implanted-group at each time point. Six months after transplantation, immunohistochemical detection of GDNF revealed strong immunoreactivity in the striatal tissue surrounding the microcapsules in the absence of tissue damage due to microcapsule implantation. No changes in the levels of dopamine and its metabolites or of tyrosine hydroxylase immunoreactivity were detected in the striatum. In summary, the implantation of microencapsulated GDNF secreting cells allows the delivery of this molecule into the rat striatum for at least 6 months and results in substantial behavioral improvement. |
| Databáze: | OpenAIRE |
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