Embryonic stem cell-derived astrocytes: a novel gene therapy vector for brain tumors.

Mahmud Uzzaman, Ronald Benveniste, Gordon Keller, Isabelle M. Germano

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

OBJECT: For gene therapy strategies currently in clinical trials, viral vectors are used to deliver transgenes directly to normal and tumor cells within the central nervous system (CNS). The use of viral vectors is limited by several factors. The aim of this study was to assess whether embryonic stem cell (ESC)-derived astrocytes expressing a doxycyclineinducible transgene can be used as a vector for gene therapy. METHODS: The authors generated a pure population of ESC-derived astrocytes carrying a transgene, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), inserted in the chromosome under the control of a highly regulated doxycycline-inducible expression system. Fully differentiated ESC-derived astrocytes were stereotactically transplanted in the mouse brain, and then cell migration and transgene expression were studied. RESULTS: The ESC-derived astrocytes started to migrate from the transplant site 48 hours after the procedure. They were found to have migrated throughout the brain tissue by 6 weeks. Transplanted ESC-derived astrocytes expressed the TRAIL transgene after doxycycline induction throughout the duration of the experiment. Teratoma formation was not observed in long-term experiments (12 weeks). CONCLUSIONS: These data show that ESC-derived astrocytes can be used as delivery vectors for CNS tumors. This technique might have a major impact on the treatment of patients with malignant gliomas and a wide spectrum of other neurological diseases.

Original languageEnglish
JournalNeurosurgical Focus
Volume19
Issue number3
StatePublished - Jan 1 2005
Externally publishedYes

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Embryonic Stem Cells
Brain Neoplasms
Astrocytes
Genetic Therapy
Transgenes
Doxycycline
Central Nervous System Neoplasms
Teratoma
Brain
Glioma
Cell Movement
Central Nervous System
Tumor Necrosis Factor-alpha
Chromosomes
Clinical Trials
Apoptosis
Ligands
Transplants
Population
Neoplasms

Cite this

Embryonic stem cell-derived astrocytes : a novel gene therapy vector for brain tumors. / Uzzaman, Mahmud; Benveniste, Ronald; Keller, Gordon; Germano, Isabelle M.

In: Neurosurgical Focus, Vol. 19, No. 3, 01.01.2005.

Research output: Contribution to journalArticle

Uzzaman, Mahmud ; Benveniste, Ronald ; Keller, Gordon ; Germano, Isabelle M. / Embryonic stem cell-derived astrocytes : a novel gene therapy vector for brain tumors. In: Neurosurgical Focus. 2005 ; Vol. 19, No. 3.
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