Petersen A, Hansson O, Emgård M, Brundin P
Section for Neuronal Survival, Wallenberg Neuroscience Center, Department of Physiological Sciences, Lund University, Sweden.
Cell Transplant. 2000 Sep-Oct;9(5):577-84. doi: 10.1177/096368970000900503.
Transplantation of embryonic ventral mesencephalon is a potential therapy for patients with Parkinson's disease. As only around 5-10% of embryonic dopaminergic neurons survive grafting into the adult striatum, it is considered necessary to use multiple donor embryos. To increase the survival of the grafted dopaminergic neurons, the clinical transplantation program in Lund currently employs the lipid peroxidation inhibitor, tirilazad mesylate, in all solutions used during tissue storage, preparation, and transplantation. However, the difficulty in obtaining a sufficient number of donor embryos still remains an important limiting factor for the clinical application of neural transplantation. In many clinical transplantation programs, it would be a great advantage if human nigral donor tissue could be stored for at least 1 week. This study was performed in order to investigate whether storage of embryonic tissue at 4 degrees C for 8 days can be applied clinically without creating a need to increase the number of donors. We compared the survival of freshly grafted rat nigral tissue, prepared according to the clinical protocol, with tissue transplanted after hibernation. Thus, in all groups tirilazad mesylate was omnipresent. One group of rats was implanted with fresh tissue and three groups with hibernated tissue with or without addition of glial cell line-derived neurotrophic factor (GDNF) in the hibernation medium and/or the final cell suspension. Earlier studies have suggested that GDNF improves the survival of hibernated nigral transplants. We found no statistically significant difference between the groups regarding graft survival after 3 weeks. However, there was a nonsignificant trend for fewer surviving dopaminergic neurons in grafts from hibernated tissue compared to fresh controls. Furthermore, we show that the addition of GDNF to the hibernation medium and/or to the final cell suspension does not significantly increase the survival of the dopaminergic neurons.
胚胎腹侧中脑移植是帕金森病患者的一种潜在治疗方法。由于只有约5 - 10%的胚胎多巴胺能神经元在移植到成年纹状体后存活，因此认为有必要使用多个供体胚胎。为了提高移植的多巴胺能神经元的存活率，隆德的临床移植项目目前在组织储存、制备和移植过程中使用的所有溶液中都加入了脂质过氧化抑制剂甲磺酸盐替拉扎德。然而，获得足够数量供体胚胎的困难仍然是神经移植临床应用的一个重要限制因素。在许多临床移植项目中，如果人类黑质供体组织能够储存至少1周，将是一个很大的优势。本研究旨在调查4℃下胚胎组织储存8天是否可在临床上应用而无需增加供体数量。我们将根据临床方案制备的新鲜移植大鼠黑质组织的存活率与冬眠后移植的组织进行了比较。因此，在所有组中都普遍存在甲磺酸盐替拉扎德。一组大鼠植入新鲜组织，三组大鼠植入冬眠组织，冬眠培养基和/或最终细胞悬液中添加或不添加胶质细胞系源性神经营养因子（GDNF）。早期研究表明，GDNF可提高冬眠黑质移植的存活率。我们发现3周后各组之间在移植物存活方面没有统计学上的显著差异。然而，与新鲜对照组相比，冬眠组织移植物中存活的多巴胺能神经元数量有减少的非显著趋势。此外，我们表明在冬眠培养基和/或最终细胞悬液中添加GDNF不会显著提高多巴胺能神经元的存活率。
