Cellular replacement therapy for neurologic disorders: potential of genetically engineered cells

✍ Scribed by Lan S. Chen; Jasodhara Ray; Lisa J. Fisher; Michael D. Kawaja; Malcolm Schinstine; Un Jung Kang; Fred H. Gage

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 622 KB
• Volume: 45
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240450305

✦ Synopsis

Abstract

Neural transplantation, a mode of cellular replacement, has been used as a therapeutic trial for Parkinson's disease. Studies indicate that tonic release of the metabolites from the graft that can be utilized by the host brain, is likely to be the major mechanism responsible for the therapeutic effect. The use of fetal tissue is complicated by ethical controversy and immunological incompatibility. Autografting adult tissue has not been successful mainly due to poor survival. Genetically engineered cells are promising alternative sources of donor cells. We have investigated the potential of primary skin fibroblasts as donor cells for intracerebral grafting. Primary skin fibroblasts survive in the brain and remain in situ. A number of genes (nerve growth factor, tyrosine hydroxylase, glutamic acid decarboxylase, and choline acetyltransferase) have been successfully introduced and expressed in the primary fibroblasts. The L‐dopasecreting primary fibroblasts exhibited a behavioral effect in a rat model of Parkinson's disease up to 8 weeks after being grafted into denervated striatum. Factors that can maximize gene transfer, transgene expression, and fibroblast survival in the brain make up the future direction of investigation.