1999 Fiscal Year Final Research Report Summary
Development of brain-targetted cell therapy using microglia as a vehicle Application to the ischaemia
| Project/Area Number |
10671329
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Fujjita Health University |
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Principal Investigator |
IMAI Fumihiro Fujita Health University, Nerosurgery, Assist. Prof, 医学部, 講師 (20288476)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Microglia / Blood brain barrier / Cell therapy / Ischaemia / Gene therapy / Drug delivery system |
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| Research Abstract |
We examined the possibility that microglia can deliver the gene of interest to brain without any effect to other organs, by injecting of microglia transfected β-galactosidase gene expression vector to the circulation. The intro-arterial injection of microglia transfected with the LacZ gene, resulted in the expression of β-galactosidase at 48 h and activity of β-galactosidase was detected for up to 3 weeks post-injection. More than 30-fold higher activity of β-galactosidase was detected in the brain than in the liver, lung or spleen at 48th post-injection. This method allows us to easily deliver the gene of interest to the brain without influencing other organs.
Next, we investigated migration of microglia into ischaemic brain. We compared migration of systemically injected microglia into normal brain vs. ischaemic brain using a model of ischaemic hippocampal lesion. Microglia were labeled by a fluorescent dye using our standard phagocytosis procedure of microscopic particles and then injected intra-arterially into Mongolian gerbils subjected ischaemia reperfusion neuronal injury. Delayed death of pyramidal neurons were confirmed by conventional histological analysis and dUTP nick eng labeling (TUNEL)method. Clusters of dye-tagged cells migrating into the hippocampal ischaemic lesions were confirmed histochemially to be microglia.
We also counted intact CA-1 pyramidal neurons in the brain sections with and without microglial injection, and confirmed that microglia had neurotrophic effect on ischaemic pyramidal neurons. Since peripherally injected microglia exhibit specific affinity for ischaemic brain lesions and does not exacerbate neuronal injury in the resent model, we suggest that microglia may have a potential to be used as piggy-back ride to deliver genes and/or drugs for CNS repair following transitory global ischaemic insult.
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