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

神经干细胞和周围神经组织用于脊髓修复的移植方法的建立

• 批准号: 13671492
• 负责人: SHINOMIYA Kenichi
• 金额: $ 1.66万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671492/
• 关键词: neural stem cell; peripheral nerve; transplantation; spinal cord regeneration; 細胞移動; オリゴ・デンドロサイト

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

体外扩增神经干细胞（NSCs）移植是修复损伤脊髓功能的潜在有力工具。移植治疗成功的先决条件是确定优化的实验参数，以促进移植的NSC群体在脊髓中的最大存活、广泛迁移和选择性分化。我们评估了胚胎海马和脊髓两种不同供体来源的nsc样细胞移植到新生儿脊髓后的基本特征。两种nsc样细胞的增殖和分化表型均可由体外培养的纤维细胞生长因子2 （FGF2）浓度控制。两种nsc样细胞都能在完整的新生儿脊髓环境中存活，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%的海马细胞优先分布在背侧白质上。相比之下，只有64%的脊髓细胞位于背侧白质。两种nsc样细胞在移植后均表现出向少突胶质谱系的限制表型。两种细胞混合移植显示海马源性nsc样细胞选择性存活。BrdU增殖试验显示，10%的海马细胞和7%的脊髓细胞对BrdU产生免疫反应。在移植后的一周内，大部分祖细胞通过背侧白质迁移而无增殖。本研究提示了海马体源性移植的可能性。NSCs为未成熟少突胶质细胞提供细胞来源，这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。海马体源性NSC与周围神经结合作为细胞支架可有效治疗损伤脊髓轴突再生。少

项目成果

Mitsuhiro Enomoto, Kenichi Shinomiya, Shigeo Okabe: "Migration and differentiation of neural progenitor cells from two different regions of embryonic central nervous system after transplantation into the intact spinal cord"European Journal of Neuroscience

Mitsuhiro Enomoto、Kenichi Shinomiya、Shigeo Okabe：“移植到完整脊髓后胚胎中枢神经系统两个不同区域的神经祖细胞的迁移和分化”欧洲神经科学杂志

M Enomoto, K Shinomiya and S Okabe: "Migration and differentiation of neural progenitor cells from two different regions of embryonic central nervous system after transplantation into the intact spinal cord"European Journal of Neuroscience. in press. (200

M Enomoto、K Shinomiya 和 S Okabe：“移植到完整脊髓后胚胎中枢神经系统两个不同区域的神经祖细胞的迁移和分化”欧洲神经科学杂志。

M Enomoto, S Okabe, Y Wakabayashi and K Shinomiya: "Effects of rac gene expression on migration of hippocampus-derived neural stem cells after spinal cord transplantation"The Journal of the Japanese Orthopaedic Association. 76(8). S937

M Enomoto、S Okabe、Y Wakabayashi 和 K Shinomiya：“rac 基因表达对脊髓移植后海马源性神经干细胞迁移的影响”日本骨科协会杂志。

M Enomoto, Y Wakabayashi, and K Shinomiya: "Spinal Cord Regeneration Present Situations and Future Aspects"The Journal of Japanese Society of Lumbar Spine Disorders. 8(1). 16-20

M Enomoto、Y Wakabayashi 和 K Shinomiya：“脊髓再生现状和未来方面”日本腰椎疾病学会杂志。

榎本光裕, 若林良明, 四宮謙一: "脊髄再生医療の現状と展望"日本腰痛学会雑誌. 8巻1号. 16-20 (2002)

Mitsuhiro Enomoto、Yoshiaki Wakabayashi、Kenichi Shinomiya：“脊髓再生医学的现状和前景”日本腰痛学会杂志，第 8 卷，第 1. 16-20 期（2002 年）。