CELLULAR REPLACEMENT THERAPY FOR NEUROLOGIC DISORDERS - POTENTIAL OF GENETICALLY ENGINEERED CELLS

被引:32
作者
CHEN, LS [1 ]
RAY, J [1 ]
FISHER, LJ [1 ]
KAWAJA, MD [1 ]
SCHINSTINE, M [1 ]
KANG, UJ [1 ]
GAGE, FH [1 ]
机构
[1] UNIV CALIF SAN DIEGO, DEPT NEUROSCI, M-024, LA JOLLA, CA 92093 USA
关键词
RETROVIRUS; FIBROBLAST; BRAIN GRAFTING; TYROSINE HYDROXYLASE; PARKINSONS DISEASE;
D O I
10.1002/jcb.240450305
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-dopa-secreting 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.
引用
收藏
页码:252 / 257
页数:6
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