Emerich D F, Winn S R, Christenson L, Palmatier M A, Gentile F T, Sanberg P R
CytoTherapeutics, Inc., Providence, RI 02906.
Neurosci Biobehav Rev. 1992 Winter;16(4):437-47. doi: 10.1016/s0149-7634(05)80185-x.
Transplantation of dopaminergic neurons derived from fetal or adrenal tissue into the striatum is a potentially useful treatment for Parkinson's disease (PD). Although initially promising, recent clinical studies using adrenal autografts have demonstrated limited efficacy. The use of human fetal cells, despite promising preliminary results, is complicated by tissue availability and ethical concerns. An attractive alternative is based on encapsulating dopamine-producing cells into polymer capsules prior to transplantation. Polymer capsules can be fabricated to surround the cells with a semi-permeable and immunoprotective barrier. The semi-permeable membrane allows nutrients to enter the capsule, so the encapsulated cells will survive and function, and dopamine and other low molecular weight constituents to diffuse out into the host tissue. Thus, the technique allows use of unmatched human tissue (allografts), or even animal tissue (xenografts) without immunosuppression of the recipient. Cell-loaded polymer capsules can also be retrieved if necessary or desired. The demonstration that striatal implants of encapsulated dopamine-producing cells promote behavioral recovery in rodent and primate models of PD further suggests that cellular encapsulation may be a useful strategy for ameliorating the behavioral consequences of PD.
将源自胎儿或肾上腺组织的多巴胺能神经元移植到纹状体中是一种治疗帕金森病(PD)的潜在有效方法。尽管最初前景看好,但最近使用自体肾上腺移植的临床研究显示疗效有限。使用人类胎儿细胞,尽管初步结果令人鼓舞,但因组织可用性和伦理问题而变得复杂。一种有吸引力的替代方法是在移植前将产生多巴胺的细胞封装在聚合物胶囊中。可以制造聚合物胶囊,用半透性和免疫保护屏障包围细胞。半透性膜允许营养物质进入胶囊,因此封装的细胞能够存活并发挥功能,多巴胺和其他低分子量成分则扩散到宿主组织中。因此,该技术允许使用不匹配的人类组织(同种异体移植),甚至动物组织(异种移植),而无需对受体进行免疫抑制。如果需要或期望,还可以取出装有细胞的聚合物胶囊。在帕金森病的啮齿动物和灵长类动物模型中,封装有产生多巴胺细胞的纹状体植入物可促进行为恢复,这进一步表明细胞封装可能是改善帕金森病行为后果的一种有用策略。