Cellular replacement therapy for neurologic disorders

potential of genetically engineered cells

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

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)252-257
Number of pages6
JournalJournal of Cellular Biochemistry
Volume45
Issue number3
DOIs
StatePublished - 1 Jan 1991

Fingerprint

Fibroblasts
Nervous System Diseases
Brain
Parkinson Disease
Skin
Tissue
Gene transfer
Therapeutics
Glutamate Decarboxylase
Choline O-Acetyltransferase
Autologous Transplantation
Tyrosine 3-Monooxygenase
Therapeutic Uses
Nerve Growth Factor
Metabolites
Transgenes
Grafts
Genes
Rats
Fetus

Keywords

  • brain grafting
  • fibroblast
  • Parkinson's disease
  • retrovirus
  • tyrosine hydroxylase

Cite this

Chen, Lan S. ; Ray, Jasodhara ; Fisher, Lisa J. ; Kawaja, Michael D. ; Schinstine, Malcolm ; Kang, Un Jung ; Gage, Fred H. / Cellular replacement therapy for neurologic disorders : potential of genetically engineered cells. In: Journal of Cellular Biochemistry. 1991 ; Vol. 45, No. 3. pp. 252-257.
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Cellular replacement therapy for neurologic disorders : potential of genetically engineered cells. / Chen, Lan S.; Ray, Jasodhara; Fisher, Lisa J.; Kawaja, Michael D.; Schinstine, Malcolm; Kang, Un Jung; Gage, Fred H.

In: Journal of Cellular Biochemistry, Vol. 45, No. 3, 01.01.1991, p. 252-257.

Research output: Contribution to journalArticleResearchpeer-review

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