Nature Medicine
3, 1129 - 1132 (1997)
doi:10.1038/nm1097-1129
Testis-derived Sertoli cells have a trophic effect on dopamine neurons and alleviate hemiparkinsonism in ratsPaul R. Sanberg1, 2, Cesario V. Borlongan1, 4, Agneta I. Othberg1, Samuel Saporta1, 2, 3, Thomas B. Freeman1, 2
& Don F. Cameron1, 2, 3
1Division of Neurological Surgery and the Neuroscience Program, University of South Florida College of Medicine, MDC Box 16, 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, USA
2Departments of Surgery, Neurology, Psychiatry, and Pharmacology, University of South Florida College of Medicine, MDC Box 16, 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, USA and
3Department of Anatomy, University of South Florida College of Medicine, MDC Box 16, 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, USA
4Department of Anatomy & Cell Biology, F. Edward School of Medicine, Uniformed Services University of Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814−4799, USA Correspondence should be addressed to P.R.S. Neural tissue transplantation has become an alternative treatment for Parkinson's disease (PD)1,2 and other neurodegenerative disorders. The clinical use of neural grafts as a source of dopamine for Parkinson's disease patients, although beneficial, is associated with logistical and ethical issues. Thus, alternative graft sources have been explored including polymer-encapsulated cells and nonneural cells (that is, adrenal chromaffin cells) or genetically modified cells that secrete dopamine and/or trophic factors3−5. Although progress has been made, no current alternative graft source has ideal characteristics for transplantation. Emerging evidence suggests the importance of trophic factors in enhancing survival and regeneration of intrinsic dopa-minergic neurons6. 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 have been shown to secrete CD-95 liqand7 and regulatory proteins8, as well as trophic, tropic, and immunosuppressive factors9,10 that provide the testis, in part, with its "immunoprivileged" status. The present study demonstrated that transplantation of rat testis-derived Sertoli cells into adult rat brains ameliorated behavioral deficits in rats with 6-hydroxydopamine-induced hemiparkinsonism. This was associated with enhanced tyrosine hydroxylase (TH) immunoreactivity in the striatum in the area around the transplanted Sertoli cells. Furthermore, in vitro experiments demonstrated enhanced dopaminergic neuronal survival and outgrowth when embryonic neurons were cultured with medium in which rat Sertoli cells had been grown. Transplantation of Sertoli cells may provide a useful alternative treatment for PD and other neurodegenerative disorders.
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