Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research, University of Oslo, Oslo, Norway.
Neurosurgery. 2011 Jan;68(1):213-22; discussion 222. doi: 10.1227/NEU.0b013e3181fd2c11.
The adult human brain contains neural stem/progenitor cells (AHNPCs) that can survive transplantation into the adult rat brain, migrate toward a lesion, and display limited neuronal differentiation in vivo.
To investigate the effect of manipulating AHNPCs before grafting by predifferentiation, ie, initiating neuronal differentiation before transplantation, and to determine whether this cell priming would affect their ability to migrate in vivo.
AHNPCs were prepared from temporal lobe resections for epilepsy. Seven days after global brain ischemia, predifferentiated AHNPCs (exposed to basic fibroblast growth factor, heparin, and laminin) were transplanted to the left hippocampus. Four and 10 weeks after transplantation, brain sections were analyzed by immunohistochemistry.
Transplanted primed cells expressed committed neuronal markers at a much earlier stage compared with nonprimed AHNPCs and were found colabeled with human markers within the damaged CA1 region 4 weeks after grafting. Furthermore, predifferentiated AHNPCs migrated preferentially into an ischemic lesion, similar to their undifferentiated counterparts. The chemoattractant effect from the expression of stromal cell-derived factor-1α (SDF-1α) in ischemic CA1 on AHNPCs expressing CXC chemokine receptor 4 (CXCR4) may explain this preference in migration in vivo.
The plasticity of neural progenitors derived from the adult human brain may be greater than previously assumed in that manipulation before grafting may influence the phenotypes seen in vivo. The SDF-1α-CXCR4 axis is involved in the targeted migration toward an ischemic lesion in the adult rat brain, similar to previous reports on endogenous progenitors in rats and grafted fetal human neural progenitors.
成人脑中含有神经干细胞/祖细胞（AHNPCs），这些细胞在移植到成年大鼠脑内后能够存活、向损伤部位迁移，并在体内进行有限的神经元分化。
通过预分化（即在移植前启动神经元分化）来研究移植前操纵 AHNPCs 的效果，并确定这种细胞预刺激是否会影响它们在体内迁移的能力。
从癫痫患者的颞叶切除物中制备 AHNPCs。在全脑缺血 7 天后，将预分化的 AHNPCs（暴露于碱性成纤维细胞生长因子、肝素和层粘连蛋白）移植到左侧海马体。在移植后 4 周和 10 周，通过免疫组织化学分析脑切片。
与未预刺激的 AHNPCs 相比，移植的预刺激细胞更早地表达了定向神经元标记物，并且在移植后 4 周内可在受损的 CA1 区内与人类标记物共标记。此外，预分化的 AHNPCs 优先迁移到缺血性病变中，这与它们未分化的同类物相似。在表达基质细胞衍生因子-1α（SDF-1α）的缺血性 CA1 中，对表达 CXC 趋化因子受体 4（CXCR4）的 AHNPCs 可能具有趋化作用，这可能解释了体内迁移的这种偏好。
源自成人脑的神经前体细胞的可塑性可能比之前认为的要大，因为移植前的操作可能会影响体内观察到的表型。SDF-1α-CXCR4 轴参与了成年大鼠脑内缺血性病变的靶向迁移，这与之前关于大鼠内源性祖细胞和移植的胎鼠神经前体细胞的报告相似。
