Han Steve S W, Kang Diana Y, Mujtaba Tahmina, Rao Mahendra S, Fischer Itzhak
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129, USA [corrected].
Exp Neurol. 2002 Oct;177(2):360-75. doi: 10.1006/exnr.2002.7995.
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.
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力，因此是中枢神经系统损伤后细胞替代治疗的候选细胞。它们在体内的表型命运取决于植入部位，这表明环境对神经元和神经胶质谱系具有不同的影响。特别是，当植入成年脊髓时，NSCs会局限于神经胶质谱系，这表明宿主脊髓环境不允许神经元分化。为了确定神经元分化受到抑制的阶段，我们研究了源自转基因碱性磷酸酶大鼠胚胎脊髓的神经元限制性前体细胞（NRP）在移植到成年脊髓后的存活、分化和整合情况。我们发现，移植的NRP细胞可分化为成熟神经元，存活至少1个月，似乎整合到宿主脊髓中，并在灰质和白质中延伸突起。相反，移植的神经胶质限制性前体细胞不会分化为神经元。我们没有观察到移植的NRP细胞发生神经胶质分化，这表明它们在体内保留了神经元限制性特性。我们得出结论，成年非神经源性中枢神经系统环境不支持多能NSCs向神经元定向阶段的转变，但确实允许NRP细胞的存活、成熟和整合。
