Widespread Striatal Delivery of GDNF from Encapsulated Cells Prevents the Anatomical and Functional Consequences of Excitotoxicity

Autor: Yaping Chu, Chris Thanos, Giovanna Paolone, Jeffrey H. Kordower, Dwaine F. Emerich, Lars Wahlberg, Briannan Bintz
Rok vydání: 2018
Předmět:
Male
Article Subject
Swine
animal diseases
Excitotoxicity
Neural degeneration
Striatum
medicine.disease_cause
glial cell line derived neurotrophic factor
Neuroprotection
lcsh:RC321-571
Cell Line
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Drug Delivery Systems
Neurotrophic factors
Glial cell line-derived neurotrophic factor
medicine
Animals
Humans
Glial Cell Line-Derived Neurotrophic Factor
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
030304 developmental biology
Neurons
0303 health sciences
biology
business.industry
urogenital system
Neurodegenerative Diseases
encapsulated cell therapy
Cell Encapsulation
Quinolinic Acid
Corpus Striatum
Neuroprotective Agents
Neurology
chemistry
nervous system
biology.protein
LLC-PK1 Cells
Neurology (clinical)
glial cell line derived neurotrophic factor
quinolinic acid
encapsulated cell therapy
business
Neuroscience
030217 neurology & neurosurgery
Neurotrophin
Quinolinic acid
Research Article
Zdroj: Neural Plasticity
Neural Plasticity, Vol 2019 (2019)
ISSN: 1687-5443
Popis: Methods. Human ARPE-19 cells engineered to secrete high levels of the glial cell line-derived neurotrophic factor (GDNF) were encapsulated into hollow fiber membranes. The devices were implanted into the rat striatum 1 week prior to striatal quinolinic acid injections. Animals were evaluated using a battery of validated motor tests, and histology was performed to determine the extent of GDNF diffusion and associated prevention of neuronal cell loss and behavioral deficits. Results. Encapsulated cell-based delivery of GDNF produced widespread distribution of GDNF throughout the entire implanted striatum. Stereological estimates of striatal neuron number and volume of lesion size revealed that GDNF delivery resulted in near complete neuroprotection. Conclusions. Delivery of neurotrophic molecules such as GDNF using encapsulated cells has reached a technological point where clinical evaluation is justified. Because GDNF has been effective in animal models of Parkinson’s disease, stroke, epilepsy, and Huntington’s disease, among other debilitating neurodegenerative diseases, encapsulated cell-based delivery of GDNF might represent one innovative means of slowing the neural degeneration seen in a myriad of currently untreatable neurological diseases.
Databáze: OpenAIRE
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