Evaluation of Reaction of Primate Brain to Grafted PC12 Cells
Evaluation of Reaction of Primate Brain to Grafted PC12 Cells
复制标题
灵长类动物脑对移植 PC12 细胞反应的评价
DOI：
10.1177/096368979900800413
复制
发表时间：
1999
影响因子：
3.3
通讯作者：
T. Ohmoto
中科院分区：
文献类型：
--
作者：
Hideyuki Yoshida;I. Date;T. Shingo;Kenjiro Fujiwara;Y. Miyoshi;T. Furuta;T. Ohmoto
纹状体内植入的聚合物封装的PC 12细胞，这构成了多巴胺能细胞系来自大鼠嗜铬细胞瘤，已被证明是有用的，改善帕金森病的症状，在几种动物。在考虑这项技术的临床应用时，我们应该确保在包膜破裂的情况下，PC 12细胞完全被宿主免疫系统排斥。在本研究中，未封装的PC 12细胞被注射到日本猴（Macaca fuscata）的脑中。移植后1、2、4和8周进行组织学[苏木精-伊红（H&E），Nissl]和免疫细胞化学[酪氨酸羟化酶（TH）和胶质细胞酸性蛋白（GFAP）]分析。此外，将包封的PC 12细胞移植到另一组日本猴的脑中，以研究宿主对胶囊的反应，并确认包封的PC 12细胞在宿主脑中继续存活。移植后2、4、8周行H&E和GFAP染色。用高效液相色谱法测定L-DOPA和多巴胺从胶囊中的释放。在未包封和包封的PC 12细胞移植组中进行磁共振成像。尽管异种移植的未包封的细胞在植入后1周和2周形成了小簇，但在4周和8周时分别保留了非常少和没有存活的PC 12细胞。宿主对异种移植物的反应逐渐减弱。发现从宿主脑取回的包封的PC 12细胞在植入后甚至8周持续释放L-DOPA和多巴胺。宿主对装载有PC 12的胶囊的反应比对未封装的PC 12细胞的反应弱得多，并且随着时间的推移而降低。这些结果表明，微囊化PC 12细胞移植是治疗帕金森病的有效和安全的策略。
Intrastriatal implantation of polymer-encapsulated PC12 cells, which constitute a dopaminergic cell line derived from rat pheochromocytoma, has proved useful for ameliorating parkinsonian symptoms in several kinds of animals. In considering the clinical application of this technique, we should make sure that PC12 cells are rejected completely by the host immune system in case the capsule breaks. In the present study, unencapsulated PC12 cells were injected into the brain of Japanese monkeys (Macaca fuscata). Histological [hematoxylin-eosin (H&E), Nissl] and immunocytochemical [tyrosine hydroxylase (TH), and glial fibrillary acidic protein (GFAP)] analyses were performed 1, 2, 4, and 8 weeks after transplantation. Also, encapsulated PC12 cells were transplanted into the brain of another group of Japanese monkeys to investigate the host reaction to the capsule and to confirm that the encapsulated PC12 cells continue to survive in the host brain. H&E and GFAP staining were performed 2, 4, and 8 weeks after transplantation. L-DOPA and dopamine release from the explanted capsules was measured by high performance liquid chromatography. Magnetic resonance imaging was performed in both unencapsulated and encapsulated PC12 cell grafted groups. Although the xenografted unencapsulated cells formed a small cluster at 1 and 2 weeks after implantation, very few and no viable PC12 cells remained at 4 and 8 weeks, respectively. The reaction of the host towards the xenograft gradually decreased. Encapsulated PC12 cells retrieved from the host brain were found to release L-DOPA and dopamine continuously even 8 weeks after implantation. The host reaction to the PC12-loaded capsule was much weaker than that to the unencapsulated PC12 cells, and decreased with time. These results indicate that encapsulated PC12 cell transplantation is an effective and safe strategy for the treatment of Parkinson's disease.