Treatment of spinal cord injury by transplantation of fetal neural precursor cells engineered to express BMP inhibitor
Treatment of spinal cord injury by transplantation of fetal neural precursor cells engineered to express BMP inhibitor
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DOI：
10.1016/j.expneurol.2003.12.007
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发表时间：
2004-09
影响因子：
5.3
通讯作者：
T. Setoguchi;K. Nakashima;T. Takizawa;M. Yanagisawa;W. Ochiai;M. Okabe;K. Yone;S. Komiya;T. Ta
中科院分区：
文献类型：
--
作者：
T. Setoguchi;K. Nakashima;T. Takizawa;M. Yanagisawa;W. Ochiai;M. Okabe;K. Yone;S. Komiya;T. Ta
脊髓损伤后的自然恢复是有限的。将神经前体细胞（NPC）移植到损伤的成年大鼠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，移植的神经前体细胞适当分化为脊髓再生所需的细胞系是重要的。为了调节移植细胞的命运，我们提倡移植基因修饰的神经前体细胞。我们证明，基因修饰，以抑制骨形态发生蛋白（BMP）信号的头蛋白表达促进分化的神经前体细胞成神经元和少突胶质细胞，除了星形胶质细胞移植后。此外，当移植表达noggin的神经前体细胞时，观察到脊髓损伤的受体小鼠的功能恢复。这些观察结果表明，基因修饰的神经前体细胞，表达参与细胞命运调节的分子，可以改善中枢神经系统（CNS）的再生。
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.