Yang Ming, Stull Natalie D, Berk Mathew A, Snyder Evan Y, Iacovitti Lorraine
Department of Neurology, Thomas Jefferson University Medical College, 1025 Walnut Street, Philadelphia, Pennsylvania 19107, USA.
Exp Neurol. 2002 Sep;177(1):50-60. doi: 10.1006/exnr.2002.7989.
The ability to differentiate neural stem cells (NSCs) into dopamine neurons is fundamental to their role in cell replacement therapies for neurodegenerative disorders such as Parkinson's disease. We show here that when a clonal line (C17.2) of undifferentiated NSCs is transplanted into the intact or 6-hydroxydopamine-lesioned striatum, cells withdraw from the cell cycle (BrdU(-)), migrate extensively in the host striatum, and express markers associated with neuronal (beta-tubulin III(+), NSE(+), NeuN(+)) but not glial (GFAP(-), MBP(-), A2B5(-)) differentiation. Importantly, by 2-5 weeks postgrafting, in the majority of these transplants, nearly all engrafted cells express the dopamine-synthesizing enzymes tyrosine hydroxylase and aromatic L-amino decarboxylase, sometimes resulting in changes in motor behavior. In contrast, no NSCs stain for dopamine-beta-hydroxylase, choline acetyltransferase, glutamic acid decarboxylase, or serotonin. We conclude that, following transplantation into the intact or 6-hydroxydopamine-lesioned rat, the adult brain contains intrinsic cues sufficient to direct the specific expression of dopaminergic traits in immature multipotential neural stem cells.
将神经干细胞（NSCs）分化为多巴胺神经元的能力，对于它们在诸如帕金森病等神经退行性疾病的细胞替代疗法中的作用至关重要。我们在此表明，当未分化的神经干细胞克隆系（C17.2）被移植到完整的或6-羟基多巴胺损伤的纹状体中时，细胞退出细胞周期（BrdU阴性），在宿主纹状体内广泛迁移，并表达与神经元分化相关的标志物（β-微管蛋白III阳性、神经元特异性烯醇化酶阳性、神经元细胞核抗原阳性），但不表达与胶质细胞分化相关的标志物（胶质纤维酸性蛋白阴性、髓鞘碱性蛋白阴性、A2B5阴性）。重要的是，在移植后2至5周，在这些移植的大多数情况下，几乎所有植入的细胞都表达多巴胺合成酶酪氨酸羟化酶和芳香族L-氨基酸脱羧酶，有时会导致运动行为的改变。相比之下，没有神经干细胞对多巴胺-β-羟化酶、胆碱乙酰转移酶、谷氨酸脱羧酶或5-羟色胺染色。我们得出结论，在移植到完整的或6-羟基多巴胺损伤的大鼠体内后，成年大脑含有足以指导未成熟多能神经干细胞中多巴胺能特性特异性表达的内在线索。
