Sanberg P R, Borlongan C V, Othberg A I, Saporta S, Freeman T B, Cameron D F
Division of Neurological Surgery, University of South Florida College of Medicine, Tampa 33612, USA.
Nat Med. 1997 Oct;3(10):1129-32. doi: 10.1038/nm1097-1129.
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.
神经组织移植已成为治疗帕金森病（PD）和其他神经退行性疾病的一种替代疗法。将神经移植物作为帕金森病患者多巴胺的来源进行临床应用，尽管有益，但存在后勤和伦理问题。因此，人们探索了其他移植物来源，包括聚合物包裹的细胞、非神经细胞（即肾上腺嗜铬细胞）或分泌多巴胺和/或神经营养因子的基因修饰细胞。尽管已取得进展，但目前尚无理想的替代移植物来源用于移植。新出现的证据表明神经营养因子在增强内源性多巴胺能神经元的存活和再生方面具有重要作用。移植易于获取、能被中枢神经系统免疫接受且能够产生多巴胺和/或神经营养因子的细胞将是理想的选择。支持细胞已被证明能分泌CD - 95配体和调节蛋白，以及神经营养、促生长和免疫抑制因子，这些因子部分赋予了睾丸“免疫赦免”状态。本研究表明，将大鼠睾丸来源的支持细胞移植到成年大鼠脑内可改善6 - 羟基多巴胺诱导的偏侧帕金森病大鼠的行为缺陷。这与移植支持细胞周围纹状体中酪氨酸羟化酶（TH）免疫反应性增强有关。此外，体外实验表明，当胚胎神经元与培养过大鼠支持细胞的培养基一起培养时，多巴胺能神经元的存活和生长得到增强。支持细胞移植可能为帕金森病和其他神经退行性疾病提供一种有效的替代治疗方法。
