Shi Haiyan, Gong Yanpei, Qiang Liang, Li Xiaoli, Zhang Shibo, Gao Jiawen, Li Kai, Ji Ximeng, Tian Ling, Gu Xiaosong, Ding Fei
Jiangsu Key Laboratory of Neuroregeneration and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, JS 226001, China; The Department of Pathophysiology, Medical School, Nantong University, Nantong, JS 226001, China.
Hospital Affiliated to Nantong University, Nantong, JS 226001, China.
Biomaterials. 2016 May;89:25-37. doi: 10.1016/j.biomaterials.2016.02.029. Epub 2016 Feb 23.
We have previously successfully enriched post-migratory neural crest cells (NCCs) from postnatal rat bone marrow (BM). These BM-NCCs possess glial and neuronal differentiating potential. Based on the neural crest origin of Schwann cells (SCs), in this study, we aimed at using a straightforward protocol to derive Schwann cell precursors (SCPs) from BM-NCCs. Several clonal subpopulations were isolated from BM-NCCs, displaying long-term proliferative capacity and maintaining the NCC identity. The BM-NCC clones could be induced to differentiate into SCs. In particular, clone N1 gave rise to a large and pure population of SCs. Clone N1-derived SCs demonstrated the myelinating capacity in their co-culture with primary dorsal root ganglion (DRG) neurons. The decreased expression of NCC-markers and increased expression of SC-markers were related to the differentiation state of clone N1-derived SCs. To investigate the repair-promoting effects of clone N1 on injured peripheral neurons in vitro and in vivo, on one hand, the oxygen glucose deprivation-injured DRG neurons were treated with clone N1-conditioned medium, improving the cell survival and axon growth of neurons; on the other hand, clone N1 or clone N1-derived SCs were respectively implanted to the crush sciatic nerve of rats, and clone N1 yielded the better outcome of nerve regeneration and function restoration than clone N1-derived SCs. Taken together, all the results collectively showed that clone N1 could be identified as SCPs, which might hold promise for cell therapy to improve peripheral nerve regeneration.
我们之前已成功从新生大鼠骨髓（BM）中富集迁移后的神经嵴细胞（NCCs）。这些骨髓来源的神经嵴细胞具有向神经胶质细胞和神经元分化的潜能。基于雪旺细胞（SCs）起源于神经嵴，在本研究中，我们旨在采用一种直接的方案从骨髓来源的神经嵴细胞中获得雪旺细胞前体细胞（SCPs）。从骨髓来源的神经嵴细胞中分离出了几个克隆亚群，它们具有长期增殖能力并保持神经嵴细胞的特性。骨髓来源的神经嵴细胞克隆可被诱导分化为雪旺细胞。特别是，克隆N1产生了大量且纯净的雪旺细胞群体。克隆N1来源的雪旺细胞在与初级背根神经节（DRG）神经元共培养时表现出髓鞘形成能力。神经嵴细胞标志物表达的降低和雪旺细胞标志物表达的增加与克隆N1来源的雪旺细胞的分化状态相关。为了研究克隆N1在体外和体内对损伤外周神经元的促修复作用，一方面，用克隆N1条件培养基处理氧糖剥夺损伤的DRG神经元，可提高神经元的细胞存活率和轴突生长；另一方面，将克隆N1或克隆N1来源的雪旺细胞分别植入大鼠坐骨神经压榨损伤部位，克隆N1在神经再生和功能恢复方面比克隆N1来源的雪旺细胞产生了更好的效果。综上所述，所有结果共同表明克隆N1可被鉴定为雪旺细胞前体细胞，这可能为改善外周神经再生的细胞治疗带来希望。
