Grafted lineage-restricted precursors differentiate exclusively into neurons in the adult spinal cord

Grafted lineage-restricted precursors differentiate exclusively into neurons in the adult spinal cord
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DOI:
10.1006/exnr.2002.7995
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发表时间:
2002-10-01
影响因子:
5.3
通讯作者:
Fischer, I
Fischer, I
中科院分区:
医学2区
文献类型:
--
作者:
Han, SSW;Kang, DY;Fischer, I

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多能神经干细胞(NSCs)具有分化为神经元和神经胶质细胞的潜能,因此是CNS损伤后细胞替代的候选者。它们在体内的表型命运取决于植入部位,表明环境对神经元和神经胶质谱系产生不同的影响。特别是,当移植到成人脊髓,神经干细胞被限制为神经胶质细胞谱系,表明宿主脊髓环境是不允许神经元分化。为了确定神经元分化被抑制的阶段,我们研究了移植到成年脊髓后,来自转基因碱性磷酸酶大鼠胚胎脊髓的神经元限制性前体(NRP)细胞的存活、分化和整合。我们发现移植的NRP细胞分化成成熟的神经元,存活至少1个月,似乎整合在宿主脊髓内,并在灰质和白色物质中延伸突起。相反,移植的胶质限制性前体细胞不分化成神经元。我们没有观察到神经胶质细胞分化的移植NRP细胞,表明他们保留了他们的神经元限制在体内的属性。我们的结论是,成人非神经源性中枢神经系统环境不支持多能神经干细胞的神经元承诺阶段的过渡,但允许生存,成熟,和整合的NRP细胞。(C)2002 Elsevier Science(美国)。
Multipotent neural stem cells (NSCs) have the potential to differentiate into neuronal and glial cells and are therefore candidates for cell replacement after CNS injury. Their phenotypic fate in vivo is dependent on the engraftment site, suggesting that the environment exerts differential effects on neuronal and glial lineages.. In particular, when grafted into the adult spinal cord, NSCs are restricted to the glial lineage, indicating that the host spinal cord environment is not permissive for neuronal differentiation. To identify the stage at which neuronal differentiation is inhibited we examined the survival, differentiation, and integration of neuronal restricted precursor (NRP) cells, derived from the embryonic spinal cord of transgenic alkaline phosphatase rats, after transplantation into the adult spinal cord. We found that grafted NRP cells differentiate into mature neurons, survive for at least 1 month, appear to integrate within the host spinal cord, and extend processes in both the gray and white matter. Conversely, grafted glial restricted precursor cells did not differentiate into neurons. We did not observe glial differentiation from the grafted NRP cells, indicating that they retained their neuronal restricted properties in vivo. We conclude that the adult nonneurogenic CNS environment does not support the transition of multipotential NSCs to the neuronal commitment stage, but does allow the survival, maturation, and integration of NRP cells. (C) 2002 Elsevier Science (USA) .