Transplantation of GABAergic Cells Derived from Bioreactor-Expanded Human Neural Precursor Cells Restores Motor and Cognitive Behavioral Deficits in a Rodent Model of Huntington's Disease
| Autor: | Arindom Sen, Ivar Mendez, Behnam Ahmadian Baghbaderani, D. Sadi, Leo A. Behie, Ruperto Ulalia, Nao R. Kobayashi, Marcus McLeod |
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| Rok vydání: | 2013 |
| Předmět: |
Biomedical Engineering
lcsh:Medicine Disease Motor Activity Neural Stem Cells Receptors GABA Huntington's disease Tubulin Precursor cell Animals Humans Medicine GABAergic Neurons Rats Wistar Cells Cultured gamma-Aminobutyric Acid Involuntary movement Transplantation Behavior Animal business.industry lcsh:R Cognition Rodent model Recovery of Function Cell Biology Quinolinic Acid medicine.disease Rats Disease Models Animal Huntington Disease Ki-67 Antigen Phenotype Cell Transdifferentiation GABAergic Female business Neuroscience |
| Zdroj: | Cell Transplantation, Vol 22 (2013) |
| ISSN: | 1555-3892 0963-6897 |
| Popis: | Huntington's disease (HD) is a neurodegenerative disorder that is characterized by progressive dementia, choreiform involuntary movements, and emotional deterioration. Neuropathological features include the progressive degeneration of striatal γ-aminobutyric acid (GABA) neurons. New therapeutic approaches, such as the transplantation of human neural precursor cells (hNPCs) to replace damaged or degenerated cells, are currently being investigated. The aim of this study was to investigate the potential for utilizing telencephalic hNPCs expanded in suspension bioreactors for cell restorative therapy in a rodent model of HD. hNPCs were expanded in a hydrodynamically controlled and homogeneous environment under serum-free conditions. In vitro analysis revealed that the bioreactor-expanded telencephalic (BET)-hNPCs could be differentiated into a highly enriched population of GABAergic neurons. Behavioral assessments of unilateral striatal quinolinic acid-lesioned rodents revealed a significant improvement in motor and memory deficits following transplantation with GABAergic cells differentiated from BET-hNPCs. Immunohistochemical analysis revealed that transplanted BET-hNPCs retained a GABAergic neuronal phenotype without aberrant transdifferentiation or tumor formation, indicating that BET-hNPCs are a safe source of cells for transplantation. This preclinical study has important implications as the transplantation of GABAergic cells derived from predifferentiated BET-hNPCs may be a safe and feasible cell replacement strategy to promote behavioral recovery in HD. |
| Databáze: | OpenAIRE |
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