Neural transplantation of cells expressing the anti-apoptotic gene bcl-2

Rein Anton, Jeffrey H. Kordower, Darci J. Kane, Charles H. Markham, Dale E. Bredesen

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Long-term survival of grafted neural cells is a major goal of neural transplantation, but typical survival rates of grafted fetal neurons are in the range of 5-10%. Whether the death of transplanted neural cells is apoptotic or necrotic is unknown. The expression of the proto-oncogene bcl-2 inhibits both apoptotic and necrotic neural cell death. In a 6-OHDA induced rat model of Parkinson's disease, Hoechst 33258 prelabelled conditionally immortalized nigral cells engineered to express bcl-2 were stereotactically transplanted into the striatum ipsilaterally to the lesioned nigrostriatal pathway. Sixteen rats received bcl-2 transfected cells, 15 received cells transfected with vector alone, and 12 received either a nondopaminergic cell line or were sham transplanted as controls. Four wk following transplantation, the rats with grafts containing bcl-2 expressing cells showed an approximately 43% decrease in apomorphine-induced rotational behavior. In contrast, 12% improvement occurred in the rats with transplanted cells transfected with vector alone (p < 0.05), and no improvement occurred in sham-operated animals (p < 0.05). Histological examination showed no tumor formation. Despite the difference in behavioral effect, no clear difference in Hoechst fluorescent staining or staining for TH, GFAP was noted; therefore, it is unknown at present whether the observed effect was due to a difference in survival or to increased efficacy per surviving transplanted neural cell, or both.

Original languageEnglish (US)
Pages (from-to)49-54
Number of pages6
JournalCell Transplantation
Volume4
Issue number1
DOIs
StatePublished - 1995
Externally publishedYes

Keywords

  • Apoptosis
  • bcl-2 gene
  • Cellular engineering
  • Neural transplantation
  • Parkinson's disease

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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