Aebischer P, Tresco P A, Sagen J, Winn S R
Section for Artificial Organs, Biomaterials and Cellular Technology, Brown University, Providence, RI.
Brain Res. 1991 Sep 27;560(1-2):43-9. doi: 10.1016/0006-8993(91)91212-j.
Surrounding bovine chromaffin cells by a semipermeable membrane may protect the transplanted cells from a host immune response and shield them from the inflammatory process resulting from the surgical trauma. Encapsulation of the chromaffin cells was achieved by interfacial adsorption of a polycation on a polyanionic colloid matrix in which the chromaffin cells were entrapped. Basal and potassium-evoked release of catecholamines from encapsulated bovine chromaffin cells was analyzed over a 4-week period in vitro. Norepinephrine and dopamine release remained constant over time whereas epinephrine release significantly decreased. The chromaffin cells also retained the capacity for depolarization-elicited catecholamine release 4 weeks following the encapsulation procedure. Morphological analysis revealed the presence of intact chromaffin cells with well-preserved secretory granules. Striatal implantation of chromaffin cell-loaded capsules significantly reduced apomorphine-induced rotation compared to empty polymer capsules in animals lesioned with 6-hydroxydopamine for at least 4 weeks. Intact chromaffin cells expressing tyrosine hydroxylase and dopamine-beta-hydroxylase were observed in all capsules implanted in the striatum for 4 weeks. The assessment of the clinical potential of transplanting encapsulated adrenal chromaffin cells of either allo- or xenogeneic origin for Parkinson's disease will require long-term behavioral studies. The present study suggests, however, that the polymer encapsulation procedure may offer an alternative to adrenal autografts as a source of dopaminergic tissue.
用半透膜包裹牛嗜铬细胞可以保护移植细胞免受宿主免疫反应的影响,并使其免受手术创伤引起的炎症过程。嗜铬细胞的封装是通过在聚阴离子胶体基质上界面吸附聚阳离子来实现的,嗜铬细胞被困在该基质中。在体外4周的时间内分析了封装的牛嗜铬细胞中儿茶酚胺的基础释放和钾诱发释放。随着时间的推移,去甲肾上腺素和多巴胺的释放保持恒定,而肾上腺素的释放则显著减少。在封装程序4周后,嗜铬细胞仍保留了去极化诱发儿茶酚胺释放的能力。形态学分析显示存在完整的嗜铬细胞,其分泌颗粒保存完好。与用6-羟基多巴胺损伤至少4周的动物中植入空聚合物胶囊相比,植入载有嗜铬细胞的胶囊显著减少了阿扑吗啡诱导的旋转。在纹状体中植入4周的所有胶囊中均观察到表达酪氨酸羟化酶和多巴胺-β-羟化酶的完整嗜铬细胞。评估移植同种或异种来源的封装肾上腺嗜铬细胞治疗帕金森病的临床潜力需要进行长期行为研究。然而,本研究表明,聚合物封装程序可能为肾上腺自体移植提供一种替代方法,作为多巴胺能组织的来源。