Emerich D F, Winn S R, Lindner M D
CytoTherapeutics, Inc., Providence, RI 02906, USA.
Cell Transplant. 1996 Sep-Oct;5(5):589-96. doi: 10.1177/096368979600500508.
To date, few studies have systematically evaluated the most appropriate location for grafting catecholaminergic cells as a potential treatment for Parkinson's disease (PD). The following study was conducted to determine 1) if placement of catecholamine-secreting encapsulated PC12 cells into the lateral ventricle of 6-OHDA-treated rats is as effective as intrastriatal implants on reducing apomorphine-induced rotational behavior, and 2) to determine if the survival of encapsulated PC12 cells is differentially affected by the implant site. Polymerencapsulated PC12 cells were implanted into either the striatum or lateral ventricle of unilateral 6-OHDA-lesioned rats. Animals were tested for apomorphine-induced rotations over a 6-wk period. Only those animals that received intrastriatal implants of encapsulated PC12 cells showed a reduction in rotation behavior. Moreover, removal of the devices from the striatum resulted in a return to preimplant rotation levels. Postexplant neurochemical analyses demonstrated that the potassium-evoked L-dopa device output increased in vivo while the potassium-evoked dopamine output from the devices decreased over time in vivo. The location of the implant significantly affected catecholamine output from the PC12 cell-loaded devices. The increase in potassium-evoked L-dopa output was greatest, as was the decrease in potassium-evoked dopamine output, from those devices implanted in the striatum. Basal output of dopamine and DOPAC was also significantly higher from devices explanted from the lateral ventricle. These results demonstrate that the continued presence of intrastriatal implants of encapsulated PC12 cells is required to maintain the behavioral effects in 6-OHDA-lesioned rats. In addition, the site of implantation appears to affect device output. These results provide additional support for intraparenchymal delivery of L-dopa and dopamine via polymer encapsulation as a possible treatment for PD.
迄今为止，很少有研究系统地评估将儿茶酚胺能细胞移植到最合适的位置作为帕金森病（PD）潜在治疗方法的效果。以下研究旨在确定：1）将分泌儿茶酚胺的包封PC12细胞植入6-OHDA处理大鼠的侧脑室，在减少阿扑吗啡诱导的旋转行为方面是否与纹状体内植入同样有效；2）确定植入部位是否对包封PC12细胞的存活有不同影响。将聚合物包封的PC12细胞植入单侧6-OHDA损伤大鼠的纹状体或侧脑室。在6周的时间内对动物进行阿扑吗啡诱导旋转测试。只有那些接受纹状体内植入包封PC12细胞的动物旋转行为有所减少。此外，从纹状体取出装置后，旋转行为恢复到植入前的水平。植入物取出后的神经化学分析表明，钾诱发的左旋多巴装置输出在体内增加，而装置中钾诱发的多巴胺输出在体内随时间下降。植入部位显著影响装载PC12细胞的装置的儿茶酚胺输出。钾诱发的左旋多巴输出增加最大的是植入纹状体的装置，钾诱发的多巴胺输出下降也是如此。从侧脑室取出的装置中多巴胺和DOPAC的基础输出也显著更高。这些结果表明，在6-OHDA损伤大鼠中，需要持续存在纹状体内植入的包封PC12细胞才能维持行为效应。此外，植入部位似乎影响装置输出。这些结果为通过聚合物包封进行左旋多巴和多巴胺的脑实质内递送作为PD的一种可能治疗方法提供了额外支持。
