Zhang R L, Zhang L, Zhang Z G, Morris D, Jiang Q, Wang L, Zhang L J, Chopp M
Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
Neuroscience. 2003;116(2):373-82. doi: 10.1016/s0306-4522(02)00696-6.
Adult brain subventricular zone progenitor cells undergo neurogenesis in the olfactory bulb. We tested the hypothesis that cultured adult subventricular zone progenitor cells migrate and differentiate into neurons when transplanted into the adult striatum. Cells in the adult rat subventricular zone were isolated and cultured for 8 days in medium containing basic fibroblast growth factor. These cells proliferated as assayed by bromodeoxyuridine immunostaining, and the majority of them were neuron-specific class III beta-tubulin (TuJ1) immunoreactive at 8 days of culture. These cultured cells were labeled in vitro with bromodeoxyuridine or with lipophilic dye-coated particles and were transplanted into the adult rat striatum. Twenty-eight days after transplantation, the cells migrated 0.5-1.5 mm from the midline of the graft to the surrounding host striatum. Migration of grafted cells in the host striatum was also detected on magnetic resonance imaging in living rats. Morphological analysis revealed that many of these migrated cells exhibited multibranched processes from the cell soma resembling host medium-size striatal projection neurons. Only a few astrocyte-like cells were detected. Double immunostaining showed that many bromodeoxyuridine immunoreactive cells were microtubule-associated protein 2 or immunoreactive with a mouse monoclonal antibody against neuronal nuclear protein, whereas only a few bromodeoxyuridine immunoreactive cells had glial fibrillary acidic protein immunoreactivity. Morphology of bromodeoxyuridine and microtubule-associated protein 2 immunoreactive cells was similar to those of host microtubule-associated protein 2 immunoreactive cells. These results suggest that transplanted cultured adult subventricular zone progenitor cells can migrate and differentiate in response to guidance cues within the adult striatum.
成人大脑海马下区祖细胞在嗅球中进行神经发生。我们检验了这样一个假设：培养的成人大脑海马下区祖细胞移植到成年纹状体后会迁移并分化为神经元。分离成年大鼠海马下区的细胞，并在含有碱性成纤维细胞生长因子的培养基中培养8天。通过溴脱氧尿苷免疫染色检测发现这些细胞发生了增殖，并且在培养8天时，它们中的大多数对神经元特异性III类β微管蛋白（TuJ1）呈免疫反应性。这些培养的细胞在体外用溴脱氧尿苷或亲脂性染料包被的颗粒进行标记，然后移植到成年大鼠纹状体中。移植后28天，细胞从移植块中线迁移0.5 - 1.5毫米至周围的宿主纹状体。在活体大鼠的磁共振成像中也检测到了移植细胞在宿主纹状体中的迁移。形态学分析显示，许多这些迁移的细胞从细胞体发出多分支突起，类似于宿主中等大小的纹状体投射神经元。仅检测到少数星形胶质细胞样细胞。双重免疫染色显示，许多溴脱氧尿苷免疫反应性细胞对微管相关蛋白2呈免疫反应性，或与抗神经元核蛋白的小鼠单克隆抗体呈免疫反应性，而只有少数溴脱氧尿苷免疫反应性细胞具有胶质纤维酸性蛋白免疫反应性。溴脱氧尿苷和微管相关蛋白2免疫反应性细胞的形态与宿主微管相关蛋白2免疫反应性细胞相似。这些结果表明，移植的培养成人大脑海马下区祖细胞能够在成年纹状体内的引导信号作用下迁移和分化。
