Rapid and Efficient Differentiation of Rodent Neural Stem Cells into Oligodendrocyte Progenitor Cells
Rapid and Efficient Differentiation of Rodent Neural Stem Cells into Oligodendrocyte Progenitor Cells
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DOI：
10.1159/000499364
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发表时间：
2019-06
影响因子：
2.9
通讯作者：
Shen Li;Jiao Zheng;Linlin Chai;M. Lin;Ruocheng Zeng;Jianhong Lu;Jing Bian
中科院分区：
文献类型：
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作者：
Shen Li;Jiao Zheng;Linlin Chai;M. Lin;Ruocheng Zeng;Jianhong Lu;Jing Bian
少突胶质祖细胞（OPCs）具有响应外界信号分化为髓鞘少突胶质细胞（OLs）的独特能力，因此在神经退行性疾病的细胞替代治疗中可能具有有益的作用。因此，建立一种有效的分化方法，从一些容易获得的干细胞来源中获得高纯度的OPCs和OLs具有重要意义。为了实现这一目标，在本研究中，我们提出了一种快速有效的方案，用于从小鼠神经干细胞（NSC）、大鼠NSC或小鼠胚胎干细胞衍生的神经上皮干细胞分化少突胶质细胞谱系。在含有Smoothened Agonist、碱性成纤维细胞生长因子和血小板衍生生长因子-AA的限定培养基中，OPCs可以在4-6天的时间内从上述干细胞产生，达到高达90%的细胞纯度。特别是，这些衍生的OPCs表现出高的可扩增性，并可以在3天内进一步分化为髓鞘碱性蛋白阳性的OL，或者在7天内分化为胶质细胞酸性蛋白阳性的星形胶质细胞。此外，将鼠源性神经干细胞移植到损伤的脊髓中，表明这是一种治疗脊髓损伤的可行策略。我们的研究结果表明，从啮齿动物干细胞中稳健生产OPC和OL的分化策略，这可能为脊髓损伤提供丰富的OPC来源。
Oligodendrocyte progenitor cells (OPCs) may have beneficial effects in cell replacement therapy of neurodegenerative disease owing to their unique capability to differentiate into myelinogenic oligodendrocytes (OLs) in response to extrinsic signals. Therefore, it is of significance to establish an effective differentiation methodology to generate highly pure OPCs and OLs from some easily accessible stem cell sources. To achieve this goal, in this study, we present a rapid and efficient protocol for oligodendroglial lineage differentiation from mouse neural stem cells (NSCs), rat NSCs, or mouse embryonic stem cell-derived neuroepithelial stem cells. In a defined culture medium containing Smoothened Agonist, basic fibroblast growth factor, and platelet-derived growth factor-AA, OPCs could be generated from the above stem cells over a time course of 4–6 days, achieving a cell purity as high as ∼90%. In particular, these derived OPCs showed high expandability and could further differentiate into myelin basic protein-positive OLs within 3 days or alternatively into glial fibrillary acidic protein-positive astrocytes within 7 days. Furthermore, transplantation of rodent NSC-derived OPCs into injured spinal cord indicated that it is a feasible strategy to treat spinal cord injury. Our results suggest a differentiation strategy for robust production of OPCs and OLs from rodent stem cells, which could provide an abundant OPC source for spinal cord injury.