Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Tissue Eng Regen Med. 2019 Oct;13(10):1854-1860. doi: 10.1002/term.2935. Epub 2019 Jul 30.
The ability to treat large peripheral nerve injuries may be greatly advanced if an accessible source of human myelinating cells is identified, as it overcomes one of the major limitations of acellular or synthetic nerve guides compared with autografts, the gold standard for large defect repair. Methods to derive oligodendrocyte precursor cells (OPCs) from human pluripotent stem cells have advanced to the point where they have been shown capable of myelination and are being evaluated in clinical trials. Here, we test the hypothesis that OPCs can survive and remyelinate axons in the peripheral nervous system during a repair process. Using freshly isolated OPCs from mouse post-natal brains, we engrafted these OPCs into the tibial nerve immediately after it being subjected to cryolesioning. At 1-month postengraftment, we found numerous graft-derived cells that survived in this environment, and many transplanted cells expressed Schwann cell markers such as periaxin and S100β coexpressed with myelin basic protein, whereas oligodendrocyte markers O4 and Olig2 were virtually absent. Our results demonstrate that OPCs can survive in a peripheral nervous system micro-environment and undergo niche-dependent transdifferentiation into Schwann cell-like cells as has previously been observed in central nervous system focal demyelination models, suggesting that OPCs constitute an accessible source of cells for peripheral nerve cell therapies.
如果能够找到一种可获取的人类髓鞘形成细胞来源，那么治疗大外周神经损伤的能力可能会得到极大提高，因为这克服了与自体移植物相比，无细胞或合成神经导管的主要局限性之一，自体移植物是大缺损修复的金标准。已经有方法可以从人多能干细胞中衍生出少突胶质前体细胞（OPC），这些方法已经先进到可以进行髓鞘形成，并正在临床试验中进行评估。在这里，我们测试了这样一个假设，即 OPC 可以在修复过程中存活并对周围神经系统中的轴突进行再髓鞘化。使用从小鼠出生后大脑中分离出的新鲜 OPC，我们在胫骨神经受到冷冻损伤后立即将这些 OPC 移植到其中。在移植后 1 个月，我们发现有许多在这种环境中存活下来的移植物衍生细胞，许多移植的细胞表达施万细胞标志物，如周围神经蛋白和 S100β，同时共表达髓鞘碱性蛋白，而少突胶质细胞标志物 O4 和 Olig2 则几乎不存在。我们的结果表明，OPC 可以在周围神经系统微环境中存活，并经历依赖小生境的转分化为施万细胞样细胞，这与以前在中枢神经系统局灶性脱髓鞘模型中观察到的情况相同，这表明 OPC 是周围神经细胞治疗的一种可获取的细胞来源。
