Establishment of transplantation methods by using neural stem cells and peripheral nerve tissues for spinal cord repair

体外扩增的神经干细胞(NSCs)移植是修复损伤脊髓功能的一种潜在的有力工具。成功移植治疗的前提是确定优化的实验参数，以促进脊髓内移植的NSC群体的最大存活、广泛迁移和选择性分化。我们评估了两种不同来源的NSC样细胞移植到新生脊髓后的基本特征。在体外，成纤维细胞生长因子2(FGF2)的浓度可以控制两种NSC样细胞的增殖和分化表型。这两种神经干细胞样细胞都能在完整的新生脊髓环境中存活，并在移植后不久表现出广泛的迁移行为。然而，定量分析显示，88%的海马区细胞优先分布于…。更偏向背侧白质。而脊髓背侧白质仅占脊髓细胞总数的%。移植后，两种NSC样细胞均表现出向少突胶质细胞方向的限制性表型。两种细胞类型的混合移植显示了海马区来源的神经干细胞样细胞的选择性存活。BrdU增殖实验显示，10%的海马细胞和7%的脊髓细胞呈BrdU免疫反应阳性。在移植后一周内，大多数祖细胞通过背侧白质迁移，没有增殖。本研究提示了海马区来源的移植的可能性。神经干细胞为未成熟的少突胶质细胞提供细胞来源，少突胶质细胞被认为是脊髓背侧白质再生轴突的髓鞘形成和营养支持所必需的。海马区来源的神经干细胞与周围神经相结合作为细胞支架可以有效地治疗损伤脊髓轴突的再生。较少

Transplantation of in vitro-expanded neural stem cells (NSCs) is a potentially powerful tool to repair functions of the injured spinal cord. A prerequisite for the successful transplantation therapy is identification of optimized experimental parameters that can promote maximal survival, extensive migration, and selective differentiation of the transplanted NSC population in the spinal cord.We evaluated the basic characteristics of NSC-like cells from two different donor sources, the embryonic hippocampus and spinal cord, after transplantation into the neonatal spinal cord. Proliferation and differentiation phenotypes of both NSC-like cells can be controlled by the concentration of the fibrobiast growth factor 2 (FGF2) in vitro. Both NSC-like cells can survive within the environment of the intact neonatal spinal cord and showed extensive migratory behavior shortly after transplantation. However, quantitative analysis revealed that 88% of total hippocampal cells were preferentially loca … More lized to the dorsal white matter. In contrast, only 64% of total spinal cord cells were in the dorsal white matter. Both NSC-like cells showed restricted phenotype toward the oligodendroglial lineage after transplantation. Transplantation of the mixture of two cell types revealed selective survival of hippocampus-derived NSC-like cells. BrdU proliferation assay revealed that 10% of total hippocampal cells and 7% of total spinal cord cells were immunoreactive with BrdU. A majority of progenitor cells migrated through dorsal white matter without proliferation during the period of one week after transplantation.This study indicates the possibility of transplanting hippocampus-derived. NSCs to supply the cell source for immature oligodendrocytes, which are thought to be essential for both the myelination and trophic support of regenerating axons in the dorsal white matter of the spinal cord. A combination of hippocampus-derived NSC and peripheral nerves as scaffolds of the cells could be effective treatment to regenerate axons in injured spinal cord. Less