Testis-derived Sertoli cells have a trophic effect on dopamine neurons and alleviate hemiparkinsonism in rats

Abstract

Neural tissue transplantation has become an alternative treatment for Parkinson's disease (PD) 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 factors. 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 dopaminergic neurons. 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 ligand and regulatory proteins, as well as trophic, tropic, and immunosuppressive factors 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.

Menstrual Blood Cells Display Stem Cell–Like Phenotypic Markers and Exert Neuroprotection Following Transplantation in Experimental Stroke

“…Finding the male counterpart of these stem/progenitor cells (eg, testis-derived cells) will further advance the potential for autologous transplantation. Of interest, we have shown that testis-derived Sertoli cells stand as effi cacious transplantable cells for CNS disorders [66,67], although Sertoli cells are likely not stem cells. Sex-specifi c stem cell sources may reveal an evolutionary gender difference.…”

Central Nervous System Entry of Peripherally Injected Umbilical Cord Blood Cells Is Not Required for Neuroprotection in Stroke

“…An additional weight-matched group of adult male Sprague-Dawley rats (nϭ10) served as positive controls (ie, nonstroke, nontransplanted, no drug treatment). Behavioral tests 12,14 were conducted at day 3 after stroke, and thereafter, animals were euthanized for histological analysis of HUCB cell survival. To reveal HUCB effects on cerebral infarction, a new set of animals (nϭ10 per group) was subjected to the same treatment.…”

Improved function of rat islets upon co-microencapsulation with Sertoli's cells in alginate/poly-L-ornithine

“…Transplantation of cerebral Sertoli's cells relieved symptoms in rats with pharmacologically induced hemiparkinsonism [ 14]. Moreover, allograft of unpurified Sertoli's cells, in combination with islets, beneath the kidney capsule of rats with STZ-induced diabetes significantly prolonged the achieved normoglycemia, as compared to controls receiving islet transplantation alone [13].…”

“…In particular, it has been demonstrated that Sertoli's cells improve in vitro functional competence of islets [12] while in vivo; they may also prolong islet allograft survival in animal models of diabetes mellitus [13]. Finally, intracerebral transplantation of Sertoli's cells relieved symptoms in rats with pharmacologically induced hemiparkinsonism [14].…”