Smits A, Odin P, Duan W M, Brundin P, Widner H, Heldin C H, Lindvall O, Funa K
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Cell Transplant. 1993 Mar-Apr;2(2):151-62. doi: 10.1177/096368979300200208.
The expression of platelet-derived growth factor (PDGF) was investigated in the embryonic donor tissue and surrounding host brain before and after intracerebral transplantation in a rat model of Parkinson's disease (PD). Ventral mesencephalic tissue from E13-E15 rat embryos was dissociated and implanted into adult rats with unilateral lesions of the mesostriatal dopamine system. Immunohistochemical studies showed that the majority of the grafted cells were PDGF-positive at early time points after grafting. However, the immunostaining gradually decreased, and had disappeared almost completely 3 wk after transplantation. These results were in agreement with in situ hybridization data demonstrating detectable levels of mRNA for PDGF chains in graft cells after 1, but not after 6 wk. In contrast, a large number of PDGF-immunoreactive cells was observed in the host brain adjacent to the grafts from 1 wk after transplantation, and increasing with time. Increased expression of PDGF was also observed in response to a sham-operation (injection of vehicle), although the number of PDGF-positive cells seemed lower than after grafting of embryonic tissue. Double immunofluorescence labeling of these cells with an anti-glial fibrillary acidic protein (GFAP) antiserum and a monoclonal antibody against PDGF B-chain, indicated that the PDGF-positive cells were astrocytes. The dynamic expression of PDGF in and around intrastriatal embryonic mesencephalic implants has several, potentially important, implications for graft survival and function. Glial cells could utilize the elevated levels of PDGF to proliferate in a reactive gliosis, and PDGF might also augment immune responses. It is also possible that PDGF increases the survival of, and promotes neurite outgrowth from, grafted dopaminergic neurons.
在帕金森病（PD）大鼠模型中，研究了脑内移植前后胚胎供体组织和周围宿主脑中血小板源性生长因子（PDGF）的表达。将E13 - E15大鼠胚胎的腹侧中脑组织解离后植入单侧中脑纹状体多巴胺系统损伤的成年大鼠体内。免疫组织化学研究表明，移植后早期大部分移植细胞为PDGF阳性。然而，免疫染色逐渐降低，移植后3周几乎完全消失。这些结果与原位杂交数据一致，原位杂交数据显示移植后1周移植细胞中有可检测水平的PDGF链mRNA，但6周后未检测到。相反，移植后1周起在移植部位相邻的宿主脑中观察到大量PDGF免疫反应性细胞，并随时间增加。假手术（注射赋形剂）后也观察到PDGF表达增加，尽管PDGF阳性细胞数量似乎低于胚胎组织移植后。用抗胶质纤维酸性蛋白（GFAP）抗血清和抗PDGF B链单克隆抗体对这些细胞进行双重免疫荧光标记，表明PDGF阳性细胞为星形胶质细胞。纹状体内胚胎中脑植入物及其周围PDGF的动态表达对移植物的存活和功能有几个潜在的重要影响。胶质细胞可利用升高的PDGF水平在反应性胶质增生中增殖，并且PDGF也可能增强免疫反应。PDGF还可能增加移植的多巴胺能神经元的存活并促进其神经突生长。
