NEURAL TRANSPLANTATION OF CELLS EXPRESSING THE ANTI-APOPTOTIC GENE BCL-2

Long-term survival of grafted neural cells is a major goal of neural t ransplantation, but typical survival rates of grafted fetal neurons ar e in the rage of 5-10%. Whether the death of transplanted neural cells is apoptotic or necrotic is unknown. The expression of the proto-onco gene bcl-2 inhibits both apoptotic and necrotic neural cell death. In a 6-OHDA induced rat model of Parkinson's disease, Hoechst 33258 prela belled conditionally immortalized nigral cells engineered to express b cl-2 were stereotactically transplanted into the striatum ipsilaterall y to the lesioned nigrostriatal pathway. Sixteen rats received bcl-2 t ransfected cells, 15 received cells transfected with vector alone, and 12 received either a nondopaminergic cell line or were sham transplan ted as controls. Four wk following transplantation, the rats with graf ts containing bcl-2 expressing cells showed an approximately 43% decre ase in apomorphine-induced rotational behavior. In contrast, 12% impro vement occurred in the rats with transplanted cells transfected with v ector alone (p < 0.05), and no improvement occurred in sham-operated a nimals (p < 0.05). Histological examination showed no tumor informatio n. Despite the difference in behavioral effect, non clear difference i n Hoechst fluorescent staining or staining for TH, GFAP was noted; the refore, it is unkown at present whether the observed effect was due to a difference in survival or to increased efficacy per surviving trans planted neural cell, or both.