Astrocyte line SVG-TH grafted in a rat model of Parkinson's disease

The present review describes gene transfer into the brain using extraneuron al cells with an ex vivo approach. The mild immunological reactions in the central nervous system to grafts provided the rationale and empirical basis for brain-transplantation, to replace dying cells, of potential clinical r elevance. Fetal human astrocytes were genetically engineered to express tyrosine hydr oxylase, the rate-limiting enzyme for the synthesis of catecolamines. These cells were also found to produce constitutively and secrete GDNF and inter leukins. Therefore, these cells may prove as a drug-delivery system for the treatment of neurological degenerative conditions such as Parkinson's dise ase (PD). The field of neuronal reconstruction has reached a critical thres hold and there is a need to evaluate the variables that will become critica l as the field matures. One of the needs is to characterize the neurochemic al alterations in the microenvironment in the context of grafted-host conne ctivity. This review discusses the functional effects of the pharmacologica lly-active construct, which consists of astrocytes producing L-DOPA and GDN F. The striatum in PD that lacks the dopaminergic projection from the subst antia nigra metabolizes and releases dopamine differently from normal tissu e and may react to different factors released by the grafted cells. Moreove r, neurochemicals of the host tissue may effect grafted cells as well. An u nderstanding of the way in which these neurochemicals are abnormal in PD an d their role in the grafted brain is critical to the improvement of reconst ructive strategies using cellular therapeutic strategies. (C) 1999 Elsevier Science Ltd. All rights reserved.