[Frontiers in Bioscience 11, 760-775, January 1, 2006]
Ex vivo gene therapy: transplantation of neurotrophic factor-secreting cells for cerebral ischemia
Takao Yasuhara 1, 2, Cesario V. Borlongan 2, 3, and Isao Date 1
1Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1, Shikata-cho, Okayama, 700-8558, Japan, 2Department of Neurology, Medical College of Georgia, 1120, 15th street, BI-3080, Augusta, GA, 30912, 3 Research and Affiliations Service Line, Augusta VA Medical Center, Augusta, GA 30912
TABLE OF CONTENTS
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.