Winn S R, Tresco P A, Zielinski B, Greene L A, Jaeger C B, Aebischer P
Section of Artificial Organs, Brown University, Providence, Rhode Island 02912.
Exp Neurol. 1991 Sep;113(3):322-9. doi: 10.1016/0014-4886(91)90022-5.
The motor deficits associated with Parkinson's disease may be ameliorated by intrastriatal placement of dopamine-secreting cells in a polymer capsule. Water soluble polyelectrolytes were utilized for membrane encapsulation of dopamine-secreting PC12 cells. Membrane permeability studies revealed exclusion of radiolabeled 69,000 Da albumin, whereas 30,000 Da carbonic anhydrase was able to cross the membrane. No cytolytic activity was observed following incubation of the encapsulated PC12 cells with PC12 cell-directed antiserum and fresh complement. In vitro, dopamine release and the surface area of intact cells per microcapsule, reached a plateau at 4 weeks that was maintained for at least 12 weeks. Viable PC12 cells were observed in microcapsules implanted for 4 and 8 weeks in nonlesioned guinea pig striata. The behavioral effect of intrastriatal dopamine release from microencapsulated PC12 cells was evaluated in the 6-hydroxydopamine unilaterally lesioned rat model. From 1 to 4 weeks postimplantation a significant reduction in rotation behavior under apomorphine challenge was observed with PC12 cell-loaded microcapsules as compared to empty microcapsules. Tyrosine hydroxylase immunopositive PC12 cells were observed 4 weeks postimplantation in all animals exhibiting a reduction in turning behavior. Implantation of polymer-encapsulated cells may provide a means for long-term delivery of neurotransmitters and growth factors to the nervous system.
通过将分泌多巴胺的细胞置于聚合物胶囊中并纹状体内植入，帕金森病相关的运动功能障碍可能会得到改善。水溶性聚电解质被用于对分泌多巴胺的PC12细胞进行膜包封。膜通透性研究显示，放射性标记的69,000 Da白蛋白被排斥在外，而30,000 Da的碳酸酐酶能够穿过该膜。将包封的PC12细胞与PC12细胞定向抗血清及新鲜补体孵育后，未观察到细胞溶解活性。在体外，每个微胶囊中多巴胺的释放及完整细胞的表面积在4周时达到平台期，并至少维持12周。在未受损豚鼠纹状体中植入4周和8周的微胶囊内观察到了存活的PC12细胞。在单侧6-羟基多巴胺损伤的大鼠模型中评估了微包封PC12细胞纹状体内多巴胺释放的行为学效应。与空微胶囊相比，植入含PC12细胞的微胶囊后1至4周，在阿扑吗啡激发下旋转行为显著减少。在所有旋转行为减少的动物中，植入后4周观察到酪氨酸羟化酶免疫阳性的PC12细胞。植入聚合物包封的细胞可能为向神经系统长期递送神经递质和生长因子提供一种方法。
