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

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...

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Veröffentlicht in:Neural plasticity Jg. 2019; H. 2019; S. 1 - 9
Hauptverfasser: Wahlberg, Lars U., Bintz, Briannan, Thanos, Chris, Chu, Yaping, Kordower, Jeffrey H., Emerich, Dwaine F., Paolone, Giovanna
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Cairo, Egypt Hindawi Publishing Corporation 01.01.2019
Hindawi
John Wiley & Sons, Inc
Wiley
Schlagworte:
Animals
Brain
Cell adhesion & migration
Cell Encapsulation
Cell Line
Corpus Striatum - drug effects
Drug Delivery Systems
Gene expression
Glial Cell Line-Derived Neurotrophic Factor - administration & dosage
Humans
Humidity
Immunology
LLC-PK1 Cells
Male
Morphology
Neurodegenerative Diseases - drug therapy
Neurons - drug effects
Neuroprotective Agents - administration & dosage
Quinolinic Acid - toxicity
Rats, Sprague-Dawley
Scanning electron microscopy
Skin
Swine
Denmark
ISSN:2090-5904, 1687-5443, 1687-5443
Online-Zugang:Volltext
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Zusammenfassung: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.
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Guest Editor: Jolanta Dorszewska
ISSN:2090-5904
1687-5443
1687-5443
DOI:10.1155/2019/6286197