TESTIS-DERIVED SERTOLI CELLS HAVE A TROPHIC EFFECT ON DOPAMINE NEURONS AND ALLEVIATE HEMIPARKINSONISM IN RATS

Neural tissue transplantation has become an alternative treatment for Parkinson's disease (PD)(1.2) and other neurodegenerative disorders. T he clinical use of neural grafts as a source of dopamine for Parkinson 's disease patients, although beneficial, is associated with logistica l and ethical issues. Thus, alternative graft sources have been explor ed including polymer-encapsulated cells and nonneural cells (that is, adrenal chromaffin cells) or genetically modified cells that secrete d opamine and/or trophic factors(3-5). Although progress has been made, no current alternative graft source has ideal characteristics for tran splantation. Emerging evidence suggests the importance of trophic fact ors in enhancing survival and regeneration of intrinsic dopaminergic n eurons(6). It would be desirable to transplant cells that are readily available, immunologically accepted by the central nervous system and capable of producing dopamine and/or trophic factors. Sertoli cells ha ve been shown to secrete CD-95 ligand(7) and regulatory proteins(8), a s well as trophic, tropic, and immunosuppressive factors(9,10) that pr ovide the testis, in part, with its ''immunoprivileged'' status, The p resent study demonstrated that transplantation of rat testis-derived S ertoli cells into adult rat brains ameliorated behavioral deficits in rats with 6-hydroxydopamine-induced hemiparkinsonism. This was associa ted with enhanced tyrosine hydroxylase (TH) immunoreactivity in the st riatum in the area around the transplanted Sertoli cells. Furthermore, in vitro experiments demonstrated enhanced dopaminergic neuronal surv ival and outgrowth when embryonic neurons were cultured with medium in which rat Sertoli cells had been grown. Transplantation of Sertoli ce lls may provide a useful alternative treatment for PD and other neurod egenerative disorders.