成年神经前体细胞的延迟移植可促进脊髓损伤后的髓鞘再生和神经功能恢复。

Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury.

作者信息

Karimi-Abdolrezaee Soheila, Eftekharpour Eftekhar, Wang Jian, Morshead Cindi M, Fehlings Michael G

机构信息

Division of Cell and Molecular Biology, Toronto Western Research Institute, Krembil Neuroscience Center, Toronto, Ontario, M5T 2S8, Canada.

出版信息

J Neurosci. 2006 Mar 29;26(13):3377-89. doi: 10.1523/JNEUROSCI.4184-05.2006.

Abstract

Spinal cord injury (SCI) results in loss of oligodendrocytes demyelination of surviving axons and severe functional impairment. Spontaneous remyelination is limited. Thus, cell replacement therapy is an attractive approach for myelin repair. In this study, we transplanted adult brain-derived neural precursor cells (NPCs) isolated from yellow fluorescent protein-expressing transgenic mice into the injured spinal cord of adult rats at 2 and 8 weeks after injury, which represents the subacute and chronic phases of SCI. A combination of growth factors, the anti-inflammatory drug minocycline, and cyclosporine A immunosuppression was used to enhance the survival of transplanted adult NPCs. Our results show the presence of a substantial number of surviving NPCs in the injured spinal cord up to 10 weeks after transplantation at the subacute stage of SCI. In contrast, cell survival was poor after transplantation into chronic lesions. After subacute transplantation, grafted cells migrated >5 mm rostrally and caudally. The surviving NPCs integrated principally along white-matter tracts and displayed close contact with the host axons and glial cells. Approximately 50% of grafted cells formed either oligodendroglial precursor cells or mature oligodendrocytes. NPC-derived oligodendrocytes expressed myelin basic protein and ensheathed the axons. We also observed that injured rats receiving NPC transplants had improved functional recovery as assessed by the Basso, Beattie, and Bresnahan Locomotor Rating Scale and grid-walk and footprint analyses. Our data provide strong evidence in support of the feasibility of adult NPCs for cell-based remyelination after SCI.

摘要

脊髓损伤(SCI)会导致少突胶质细胞丧失,存活轴突脱髓鞘,并造成严重的功能障碍。自发髓鞘再生有限。因此,细胞替代疗法是一种有吸引力的髓鞘修复方法。在本研究中,我们将从表达黄色荧光蛋白的转基因小鼠中分离出的成年脑源性神经前体细胞(NPCs),在损伤后2周和8周移植到成年大鼠的损伤脊髓中,这分别代表SCI的亚急性期和慢性期。使用生长因子、抗炎药物米诺环素和环孢素A免疫抑制的组合来提高移植的成年NPCs的存活率。我们的结果显示,在SCI亚急性期移植后长达10周,损伤脊髓中存在大量存活的NPCs。相比之下,移植到慢性损伤部位后的细胞存活率较低。亚急性移植后,移植的细胞向头侧和尾侧迁移超过5毫米。存活的NPCs主要沿着白质束整合,并与宿主轴突和胶质细胞紧密接触。大约50%的移植细胞形成少突胶质前体细胞或成熟少突胶质细胞。NPC衍生的少突胶质细胞表达髓鞘碱性蛋白并包裹轴突。我们还观察到,通过Basso、Beattie和Bresnahan运动评分量表以及网格行走和足迹分析评估,接受NPC移植的损伤大鼠功能恢复有所改善。我们的数据为成年NPCs用于SCI后基于细胞的髓鞘再生的可行性提供了有力证据。

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