Brain‐specific gene expression by immortalized microglial cell‐mediated gene transfer in the mammalian brain

Sawada, Makoto; Imai, Fumihiro; Suzuki, Hiromi; Hayakawa, Motoharu; Kanno, Tetsuo; Nagatsu, Toshiharu

doi:10.1016/s0014-5793(98)00879-5

Cited by 73 publications

(48 citation statements)

References 18 publications

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“…This timing is compatible with the migration time of microglia to brain, 6 the glioma image achievement and the GCV treatment. Moreover, in our model, microglia maintain their ability to stay surrounding the C6 tumor.…”

supporting

confidence: 56%

Microglia used as vehicles for both inducible thymidine kinase gene therapy and MRI contrast agents for glioma therapy

et al. 2007

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Microglia are phagocytic cells that are chemoattracted by brain tumors and can represent up to 70% of the tumor cell population. To get insight into gene therapy against glioma, we decided to take advantage of those microglia properties and to use those cells as vehicles to transport simultaneously a suicide gene (under the control of a heat-sensitive promoter) and contrast agents to localize them by magnetic resonance imaging before applying any therapeutic treatment. Thymidine kinase (TK) expression and its functionality after gancyclovir administration were investigated. After the heat shock (441C and 20 min), TK was expressed in 50% of the cells. However, after gancyclovir treatment, 90% of the cells died by apoptosis, showing an important bystander effect. Then, the cells were incubated with new lanthanide contrast agents to check both their potential toxicity and their MR properties. Results indicate that the nanoparticles did not induce any cell toxicity and yield a hypersignal on MR images at 4.7 T. These in vitro experiments indicate that microglia are good candidates as vectors in gene therapy against brain tumors. Finally, microglia containing gadolinium-grafted nanoparticles were injected in the close vicinity of C6 tumor, in a mouse. The hyperintensive signal obtained on in vivo images as well as its retention time show the potential of the novel contrast agents for cellular imaging.

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confidence: 56%

Microglia used as vehicles for both inducible thymidine kinase gene therapy and MRI contrast agents for glioma therapy

et al. 2007

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“…The microglial cell line Ra2 cells established from neonatal C57BL/6J (H-2 b ) mice using a non-enzymatic and non-virus-transformed procedure (Sawada et al 1998) were kindly provided by Dr. Sawada (Department of Brain Function, Research Institute of Environmental Medicine, Nagoya University, Nagoya). Ra2 cells proliferated in the same culture medium as primary microglia supplemented with 1 ng/ml GM-CSF.…”

Section: Preparation and Culture Of Primary Microglia And Ra2 Cell Linesmentioning

confidence: 99%

Juzen-taiho-to, an Herbal Medicine, Activates and Enhances Phagocytosis in Microglia/Macrophages

Liu

Wang

Sekiyama

et al. 2008

Tohoku J. Exp. Med.

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“…Our previous studies showed that microglia isolated from rodent mixed-brain cultures retain the ability to enter the normal brain from the circulation (Imai et al, 1997(Imai et al, , 1999Sawada et al, 1998). Hence, microglia can be introduced into the central nervous system by injection into the bloodstream in animal models of neuronal injury.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of Exogenous Microglia in Global Brain Ischemia

Imai

Suzuki

Oda

et al. 2006

J Cereb Blood Flow Metab

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Exogenous microglia pass through the blood-brain barrier and migrate to ischemic hippocampal lesions when injected into the circulation. We investigated the effect of exogenous microglia on ischemic CA1 pyramidal neurons. Microglia were isolated from neonatal mixed brain cultures, labeled with the fluorescent dye PKH26, and injected into the subclavian artery of Mongolian gerbils subjected to ischemia reperfusion neuronal injury. PKH26-labeled microglia migrated to the ischemic hippocampal lesion, resulting in increased numbers of surviving neurons compared with control animals, even when injected 24 h after ischemia. Interferon-c stimulation of isolated microglia enhanced the neuroprotective effect. Administration of exogenous microglia resulted in normal performance in a passive avoidance-learning task. Additionally, administration of exogenous microglia increased the expression of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in the ischemic hippocampus, and thus might have induced neurotrophin-dependent protective activity in damaged neurons. Peripherally injected microglia exhibited a specific affinity for ischemic brain lesions, and protected against ischemic neuronal injury in vivo. It is possible that administration of exogenous microglia can be developed as a potential candidate therapy for central nervous system repair after transitory global ischemia.

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Brain‐specific gene expression by immortalized microglial cell‐mediated gene transfer in the mammalian brain

Cited by 73 publications

References 18 publications

Microglia used as vehicles for both inducible thymidine kinase gene therapy and MRI contrast agents for glioma therapy

Microglia used as vehicles for both inducible thymidine kinase gene therapy and MRI contrast agents for glioma therapy

Juzen-taiho-to, an Herbal Medicine, Activates and Enhances Phagocytosis in Microglia/Macrophages

Neuroprotective Effect of Exogenous Microglia in Global Brain Ischemia

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