Toward Autologous ex Vivo Gene Therapy for the Central Nervous System with Human Adult Astrocytes
| Autor: | Naïma Hanoun, Michel Hamon, Jacques Philippon, Jacques Mallet, Jean-Luc Ridet, Philippe Pencalet, Olga Corti |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Cell type Tyrosine 3-Monooxygenase Cell Transplantation Transgene Genetic enhancement Genetic Vectors Biology Adenoviridae Viral vector Freezing Genetics Humans Autologous transplantation Molecular Biology Cells Cultured Aged Cerebral Cortex Regulation of gene expression Tyrosine hydroxylase Genetic Therapy Middle Aged Immunohistochemistry Cell biology Gene Expression Regulation Tetracyclines Astrocytes Immunology Molecular Medicine Cell Division Ex vivo |
| Zdroj: | Human Gene Therapy. 10:271-280 |
| ISSN: | 1557-7422 1043-0342 |
| Popis: | The combination of gene transfer techniques and cell transplantation is a promising approach to deliver therapeutic molecules into the CNS. To optimize gene transfer systems, several neural and nonneural cell types are currently under investigation. Among these cells, astrocytes are particularly well suited because of their CNS origin, their efficient secretory mechanisms, and their role as neuronal support. Most importantly, the use of human adult astrocytes as cellular vehicles for ex vivo gene transfer may open the way to autologous transplantation, thus obviating immunological rejection and the side effects of immunosuppressors. In the present study, we report the ability of these cells to be expanded and genetically modified in vitro. Astrocytes derived from human adult cerebral cortex were grown and maintained in vitro as pure primary cultures for at least 10 months. In addition, cells were efficiently transduced by an adenoviral vector encoding human tyrosine hydroxylase (hTH) under the negative control of the tetracycline-based regulatory system (tet-off). The infected cells synthesized large amounts of active hTH and released L-dopa. In addition, doxycycline, a potent analog of tetracycline, efficiently regulated transgene expression. This work is a first step toward the development of therapeutic strategies based on the use of genetically engineered human adult astrocytes for autologous transplantation in human neurodegenerative diseases and CNS trauma. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|