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神经前体细胞源性少突胶质前体细胞移植入正常和损伤脊髓后的分化。

Differentiation of neural precursor cell-derived oligodendrocyte progenitor cells following transplantation into normal and injured spinal cords.

机构信息

Department of Neurobiology, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, PR China.

出版信息

Differentiation. 2010 Nov-Dec;80(4-5):228-40. doi: 10.1016/j.diff.2010.09.179. Epub 2010 Sep 18.

Abstract

Demyelination contributes to the functional deficits after spinal cord injury (SCI). Therefore, remyelination may be an important strategy to facilitate repair after SCI. Oligodendrocyte precursor cells (OPCs) are immature oligodendrocytes and can differentiate into myelin-forming cells of central nervous system under certain conditions. OPC transplantation is an attractive approach for the treatment of demyelinating diseases. In this study, we transplanted OPCs expressing green fluorescent protein (GFP-OPCs) into normal and injured rat spinal cords to evaluate the differentiation of transplanted OPCs in vivo. Unfortunately, the grafted GFP-OPCs, in spinal cord whether normal or injured, were all differentiated into astrocytes, but not oligodendrocytes. Our further study indicated that inflammatory environment might not be the key factor influencing the differentiation of OPCs. Some spinal cord components, such as bone morphogenetic proteins (BMPs), were the major factors that induced OPCs to differentiate into astrocytes. The three types of BMP receptor (BMPRIA, IB and II) could all be detected in OPCs, and the astroglial differentiation of OPCs induced by spinal cord homogenate extract (SCHE) in vitro could be blocked partly by noggin, an antagonist of BMP. These results suggested that the BMPR signal transduction pathway might be one of the key factors which determine the differentiation direction of engrafted OPCs in spinal cord.

摘要

脱髓鞘是脊髓损伤 (SCI) 后导致功能障碍的原因之一。因此,髓鞘再生可能是 SCI 后修复的重要策略。少突胶质前体细胞 (OPC) 是不成熟的少突胶质细胞,在某些条件下可以分化为中枢神经系统的髓鞘形成细胞。OPC 移植是治疗脱髓鞘疾病的一种有吸引力的方法。在这项研究中,我们将表达绿色荧光蛋白 (GFP-OPC) 的 OPC 移植到正常和损伤的大鼠脊髓中,以评估体内移植的 OPC 分化情况。不幸的是,移植的 GFP-OPC 在正常或损伤的脊髓中均分化为星形胶质细胞,而不是少突胶质细胞。我们进一步的研究表明,炎症环境可能不是影响 OPC 分化的关键因素。一些脊髓成分,如骨形态发生蛋白 (BMPs),是诱导 OPC 分化为星形胶质细胞的主要因素。OPC 中可检测到三种 BMP 受体 (BMPRIA、IB 和 II),体外脊髓匀浆提取物 (SCHE) 诱导的 OPC 星形胶质细胞分化可被 noggin 部分阻断,noggin 是 BMP 的拮抗剂。这些结果表明,BMPR 信号转导通路可能是决定移植 OPC 在脊髓中分化方向的关键因素之一。

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