Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Cell Transplant. 2011;20(2):167-76. doi: 10.3727/096368910X522090. Epub 2010 Aug 18.
Root avulsion of the brachial plexus results in a progressive and pronounced loss of motoneurons. Cell replacement strategies have therapeutic potential in the treatment of motoneuron degenerative neurological disorders. Here, we transplanted spinal cord-derived neural progenitor cells (NPCs) into the cervical ventral horn of adult rats immediately, 2 weeks, or 6 weeks after root avulsion to determine an optimal time scale for the survival and differentiation of grafted cells. We showed that grafted NPCs survived robustly at all three time points and there was no statistical difference in survival rate. Interestingly, however, transplantation at 2 weeks postavulsion significantly increased the neuronal differentiation of transplanted NPCs compared to transplantation immediately or at 6 weeks postavulsion. Moreover, only NPCs transplanted at 2 weeks postavulsion were able to differentiate into choline acetyltransferase (ChAT)-positive neurons. Specific ELISAs and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) demonstrated that expression levels of BDNF and GDNF were significantly upregulated in the ventral cord at 2 weeks postavulsion compared to immediately or at 6 weeks postavulsion. Our study suggests that the cervical ventral horn at 2 weeks postavulsion both supports neuronal differentiation and induces region-specific neuronal generation possibly because of its higher expression of BDNF and GDNF.
臂丛神经根撕脱导致运动神经元进行性显著缺失。细胞替代策略在治疗运动神经元退行性神经疾病方面具有治疗潜力。在这里，我们在臂丛神经根撕脱后立即、2 周或 6 周将脊髓源性神经前体细胞（NPCs）移植到成年大鼠的颈腹角，以确定移植细胞存活和分化的最佳时间尺度。我们表明，移植的 NPCs 在所有三个时间点都能顽强存活，存活率没有统计学差异。然而，有趣的是，与立即或 6 周后移植相比，移植后 2 周时明显增加了移植 NPC 的神经元分化。此外，只有在 2 周后移植的 NPC 才能分化为胆碱乙酰转移酶（ChAT）阳性神经元。特异性 ELISA 和定量逆转录聚合酶链反应（RT-PCR）表明，与立即或 6 周后移植相比，2 周后移植时 BDNF 和 GDNF 的表达水平在腹侧脊髓中显著上调。我们的研究表明，臂丛神经根撕脱后 2 周时的颈腹角既支持神经元分化，又诱导特定区域的神经元生成，可能是因为其 BDNF 和 GDNF 表达水平较高。
