Ex vivo gene therapy: transplantation of neurotrophic factor-secreting cells for cerebral ischemia.
Expressions of various neurotrophic factors or their receptors fluctuate after stroke, which in part prompted investigations into the efficacy of neurotrophic factors as treatment modality for stroke. The methods to deliver neurotrophic factors into the brain can be categorized into: 1) the surgical route of administration, such as intracerebral, intraventricular, intra-arterial, or intravenous systemic administration and 2) the manipulation of the therapeutic molecules via ex vivo or in vivo techniques. With ex vivo method, genetically engineered cells, including the use of autologous cells, have been explored. In this review, the potent therapeutic applications of neurotrophic factors in stroke are described, with emphasis on ex vivo methods, especially transplantation of encapsulated stem cells modified with adenovirus. Neurotrophic factor delivery, combined with ex vivo method, poses as novel treatment for stroke, although additional safety and efficacy studies remain to be examined.
Yasuhara
Takao
T
Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, 700-8558, Japan. tyasu37@cc.okayama-u.ac.jp
Borlongan
Cesario V
CV
Date
Isao
I
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D017690:Cell Transplantation / Q000379:methods*; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism; D020521:Stroke / Q000628:therapy; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors