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通过移植经基因工程改造以表达骨形态发生蛋白抑制剂的胎儿神经前体细胞治疗脊髓损伤。

Treatment of spinal cord injury by transplantation of fetal neural precursor cells engineered to express BMP inhibitor.

作者信息

Setoguchi Takao, Nakashima Kinichi, Takizawa Takumi, Yanagisawa Makoto, Ochiai Wataru, Okabe Masaru, Yone Kazunori, Komiya Setsuro, Taga Tetsuya

机构信息

Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0081, Japan.

出版信息

Exp Neurol. 2004 Sep;189(1):33-44. doi: 10.1016/j.expneurol.2003.12.007.

Abstract

Spontaneous recovery after spinal cord injury is limited. Transplantation of neural precursor cells (NPCs) into lesioned adult rat spinal cord results in only partial functional recovery, and most transplanted cells tend to differentiate predominantly into astrocytes. In order to improve functional recovery after transplantation, it is important that transplanted neural precursor cells appropriately differentiate into cell lineages required for spinal cord regeneration. In order to modulate the fate of transplanted cells, we advocate transplanting gene-modified neural precursor cells. We demonstrate that gene modification to inhibit bone morphogenetic protein (BMP) signaling by noggin expression promoted differentiation of neural precursor cells into neurons and oligodendrocytes, in addition to astrocytes after transplantation. Furthermore, functional recovery of the recipient mice with spinal cord injury was observed when noggin-expressing neural precursor cells were transplanted. These observations suggest that gene-modified neural precursor cells that express molecules involved in cell fate modulation could improve central nervous system (CNS) regeneration.

摘要

脊髓损伤后的自发恢复是有限的。将神经前体细胞(NPCs)移植到成年大鼠受损脊髓中仅导致部分功能恢复,并且大多数移植细胞倾向于主要分化为星形胶质细胞。为了改善移植后的功能恢复,重要的是移植的神经前体细胞能够适当地分化为脊髓再生所需的细胞谱系。为了调节移植细胞的命运,我们主张移植基因修饰的神经前体细胞。我们证明,通过表达头蛋白(noggin)抑制骨形态发生蛋白(BMP)信号的基因修饰促进了神经前体细胞在移植后分化为神经元和少突胶质细胞,此外还有星形胶质细胞。此外,当移植表达头蛋白的神经前体细胞时,观察到脊髓损伤受体小鼠的功能恢复。这些观察结果表明,表达参与细胞命运调节分子的基因修饰神经前体细胞可以改善中枢神经系统(CNS)再生。

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