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Fumihiro Imai

Fumihiro Imai

Ichiriyama Imai Clinic, Japan

Title: Development of brain-targeted cell therapy using microglia

Biography

Imai completed his doctorate from Fujita Health University School of Medicine in 1990. He is the president of the Microglia laboratory, Ichiriyama Imai Clinic, and also a visiting professor of the Department of Neurosurgery, Fujita Health University. He is also joining Research Institute of Environmental Medicine Brain Functions, Nagoya University. He demonstrated that cultured microglia entered the brain from the circulation and exerted the neuro-protective effect on damaged neurons in vivo, in 2007. It is expected that his work will lead to the development of a novel minimum invasive therapy for the central nervous system diseases.

Abstract

Microglia arise from the monocyte/macrophage linage, and are ubiquitously distributed in the central nervous system, representing up to 20% of the total glial cell population in the brain. In accordance with Del Rio Hortega’s early teaching, the current view is that resident maicroglia are of mesodermal origin, derived from bone marrow precursor cells. These cells invade the central nervous system at an early embryonic stage to give rise to typical process-bearing microglia. Microglia isolated from neonatal mixed brain culture pass through the blood brain-brain barrier and migrate to ischemic hippocampal lesions when injected into the circulation. Injection of cultured microglia into the circulation of transient global ischemia animal models resulted in not only increased numbers of surviving pyramidal neurons but also maintenance of normal performance in a passive avoidance-learning task compared with control animals. We have already established nef-gene transfected microglia cell line (wild type: HS1 and mutant type A2G) and GFP expressing mouse glioblastoma cell line (GL261-GFP). We produced glioma animal models by inoculating GL261-GFP into the brain of the synergic mouse. Injection of HS1 into the circulation of glioma models significantly prolonged the survival period compared with control animals. Morphological and physiological studies indicated that injection of HS1 had no harmful effects on the recipients. To realize the brain-targeted cell therapy using microglia, we are now trying to establish the method of differentiation of microglia from iPSCs.