Baker K A, Hong M, Sadi D, Mendez I
Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada.
Exp Neurol. 2000 Apr;162(2):350-60. doi: 10.1006/exnr.1999.7337.
The clinical findings on neural transplantation for Parkinson's disease (PD) reported thus far are promising but many issues must be addressed before neural transplantation can be considered a routine therapeutic option for PD. The future of neural transplantation for the treatment of neurological disorders may rest in the discovery of a suitable alternative cell type for fetal tissue. One such alternative may be neurons derived from a human teratocarcinoma (hNT). hNT neurons have been shown to survive and integrate within the host brain following transplantation and provide functional recovery in animal models of stroke and Huntington's disease. In this study, we describe the transplantation of hNT neurons in the substantia nigra (SN) and striatum of the rat model for PD. Twenty-seven rats were grafted with one of three hNT neuronal products; hNT neurons, hNT-DA neurons, or lithium chloride (LiCl) pretreated hNT-DA neurons. Robust hNT grafts could be seen with anti-neural cell adhesion molecule and anti-neuron-specific enolase immunostaining. Immunostaining for tyrosine hydroxylase (TH) expression revealed no TH-immunoreactive (THir) neurons in any animals with hNT neuronal grafts. THir cells were observed in 43% of animals with hNT-DA neuronal grafts and all animals with LiCl pretreated hNT-DA neuronal grafts (100%). The number of THir neurons in these animals was low and not sufficient to produce significant functional recovery. In summary, this study has demonstrated that hNT neurons survive transplantation and express TH in the striatum and SN. Although hNT neurons are promising as an alternative to fetal tissue and may have potential clinical applications in the future, further improvements in enhancing TH expression are needed.
迄今为止报道的帕金森病（PD）神经移植的临床研究结果很有前景，但在神经移植成为PD的常规治疗选择之前，还有许多问题需要解决。神经移植治疗神经疾病的未来可能取决于能否发现一种适合替代胎儿组织的细胞类型。一种这样的替代细胞可能是源自人畸胎癌（hNT）的神经元。已证明hNT神经元在移植后能在宿主脑内存活并整合，并在中风和亨廷顿病动物模型中实现功能恢复。在本研究中，我们描述了hNT神经元在PD大鼠模型的黑质（SN）和纹状体中的移植。27只大鼠被移植了三种hNT神经元产物之一；hNT神经元、hNT-DA神经元或经氯化锂（LiCl）预处理的hNT-DA神经元。通过抗神经细胞黏附分子和抗神经元特异性烯醇化酶免疫染色可以看到强健的hNT移植物。酪氨酸羟化酶（TH）表达的免疫染色显示，在任何接受hNT神经元移植的动物中均未发现TH免疫反应性（THir）神经元。在43%接受hNT-DA神经元移植的动物和所有接受LiCl预处理的hNT-DA神经元移植的动物（100%）中观察到了THir细胞。这些动物中THir神经元的数量较少，不足以产生显著的功能恢复。总之，本研究表明hNT神经元在移植后存活，并在纹状体和黑质中表达TH。尽管hNT神经元作为胎儿组织的替代物很有前景，且未来可能具有潜在的临床应用，但仍需要进一步改善以增强TH表达。
