Transplantation of polymer encapsulated neurotransmitter secreting cells: effect of the encapsulation technique.
Transplantation of polymer encapsulated neurotransmitter secreting cells: effect of the encapsulation technique.
复制标题
聚合物封装神经递质分泌细胞的移植：封装技术的效果。
DOI：
10.1115/1.2891231
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Greene,LA
中科院分区：
文献类型：
--
作者：
Aebischer,P;Winn,SR;Tresco,PA;Jaeger,CB;Greene,LA
与神经系统疾病相关的缺陷可以通过在脑损伤的靶结构内移植释放缺失的神经递质的聚合物包封的细胞来改善。用适当分子量截留的选择性渗透膜包围细胞允许营养物质向内扩散和神经递质向外扩散，但阻止免疫球蛋白或免疫细胞到达移植物。因此，该技术允许跨物种移植有丝分裂后细胞。它还允许转化细胞系的神经移植，因为聚合物胶囊通过物理隔离移植的组织来防止肿瘤的形成。在本研究中，我们比较了由2种不同方法封装的多巴胺分泌细胞逆转实验性帕金森病的能力，帕金森病是一种神经退行性疾病，其特征在于多巴胺能黑质-纹状体通路变性后纹状体内缺乏多巴胺导致的运动障碍。将PC 12细胞装载在基于聚电解质的微胶囊或基于热塑性塑料的大胶囊中，并在体外维持或移植到大鼠实验性帕金森模型中4周。化学诱导的去极化增加了多巴胺的体外释放从macrocapsules随着时间的推移，而没有增加释放从微胶囊观察。包封的PC 12细胞能够减少病变引起的旋转不对称大鼠至少4周，无论使用的封装技术。用两种包封方法，PC 12细胞活力在体内比在体外更大，这表明纹状体释放PC 12细胞的营养因子。观察到更多的脑组织损伤微胶囊比macrocapsules，可能是由于难以操纵更脆弱的微胶囊。在微囊周围的脑实质中观察到类似藻酸盐的材料，而植入后4周，在基于聚（丙烯腈-氯乙烯）的胶囊中未观察到结构变化。这一事实引发了关于植入神经系统的基于聚电解质的胶囊的体内稳定性的问题。我们的结论是，植入聚合物封装的细胞可以提供一种手段，长期提供足够的封装技术的神经递质。
Deficits associated with neurological diseases may be improved by the transplantation within the brain lesioned target structure of polymer encapsulated cells releasing the missing neurotransmitter. Surrounding cells with a permselective membrane of appropriate molecular weight cut-off allows inward diffusion of nutrients and outward diffusion of neurotransmitters, but prevents immunoglobulins or immune cells from reaching the transplant. This technique therefore allows transplantation of postmitotic cells across species. It also permits neural grafting of transformed cell lines since the polymer capsule prevents the formation of tumors by physically sequestering the transplanted tissue. In the present study, we compared the ability of dopaminesecreting cells, encapsulated by 2 different methods, to reverse experimental Parkinson’s disease, a neurodegenerative disease characterized by motor disturbances due to a lack of dopamine within the striatum following degeneration of the dopaminergic nigro-striatal pathway. PC12 cells were loaded in polyelectrolyte-based microcapsules or thermoplastic-based macrocapsules and maintained in vitro or transplanted in a rat experimental Parkinson model for 4 weeks. Chemically-induced depolarization increased the in vitro release of dopamine from macrocapsules over time, while no increase in release was observed from microcapsules. Encapsulated PC12 cells were able to reduce lesion-induced rotational asymmetry in rats for at least 4 weeks, regardless of the encapsulation technique used. With both encapsulation methods, PC12 cell viability was greater in vivo than in vitro which suggests that the striatum releases trophic factors for PC12 cells. More brain tissue damage was observed with microcapsules than macrocapsules, possibly the result of the difficulty of manipulating the more fragile microcapsules. Material resembling alginate was observed in the brain parenchyma surrounding the microcapsules, whereas no structural changes were observed with poly (acrylonitrile vinyl chloride) based capsules 4 weeks post-implantation. This fact raises questions about the in vivo stability of polyelectrolyte-based capsules implanted in the nervous system. We conclude that the implantation of polymer-encapsulated cells may provide a means for long-term delivery of neurotransmitters providing adequate encapsulation technology.