Ludwig Boltzmann Institute for Experimental and Clinical Traumatology/AUVA Research Center, Vienna, Austria.
Austrian Cluster for Tissue Regeneration, Vienna, Austria.
J Peripher Nerv Syst. 2020 Mar;25(1):32-43. doi: 10.1111/jns.12365. Epub 2020 Feb 5.
The gold standard for peripheral nerve regeneration uses a sensory autograft to bridge a motor/sensory defect site. For motor nerves to regenerate, Schwann cells (SC) myelinate the newly grown axon. Sensory SCs have a reduced ability to produce myelin, partially explaining low success rates of autografts. This issue is masked in pre-clinical research by the excessive use of the rat sciatic nerve defect model, utilizing a mixed nerve with motor and sensory SCs. Aim of this study was to utilize extracorporeal shockwave treatment as a novel tool to influence SC phenotype. SCs were isolated from motor, sensory and mixed rat nerves and in vitro differences between them were assessed concerning initial cell number, proliferation rate, neurite outgrowth as well as ability to express myelin. We verified the inferior capacity of sensory SCs to promote neurite outgrowth and express myelin-associated proteins. Motor Schwann cells demonstrated low proliferation rates, but strongly reacted to pro-myelination stimuli. It is noteworthy for pre-clinical research that sciatic SCs are a strongly mixed culture, not representing one or the other. Extracorporeal shockwave treatment (ESWT), induced in motor SCs an increased proliferation profile, while sensory SCs gained the ability to promote neurite outgrowth and express myelin-associated markers. We demonstrate a strong phenotype commitment of sciatic, motor, and sensory SCs in vitro, proposing the experimental use of SCs from pure cultures to better mimic clinical situations. Furthermore we provide arguments for using ESWT on autografts to improve the regenerative capacity of sensory SCs.
周围神经再生的金标准是使用感觉神经自体移植物来桥接运动/感觉缺陷部位。为了使运动神经再生，许旺细胞（Schwann cell，SC）会对新生长的轴突进行髓鞘形成。感觉 SC 的髓鞘形成能力降低，这部分解释了自体移植物成功率低的原因。在临床前研究中，这个问题被大鼠坐骨神经缺损模型的过度使用所掩盖，该模型利用了具有运动和感觉 SC 的混合神经。本研究的目的是利用体外冲击波治疗作为一种新的工具来影响 SC 表型。从大鼠的运动、感觉和混合神经中分离出 SC，并在体外评估它们之间在初始细胞数量、增殖率、神经突生长以及表达髓鞘相关蛋白的能力方面的差异。我们验证了感觉 SC 促进神经突生长和表达髓鞘相关蛋白的能力较弱。需要注意的是，对于临床前研究，坐骨 SC 是一种强烈混合的培养物，不能代表其中一种或另一种。体外冲击波治疗（extracorporeal shock wave treatment，ESWT）诱导运动 SC 增殖率增加，而感觉 SC 获得了促进神经突生长和表达髓鞘相关标志物的能力。我们在体外证明了坐骨、运动和感觉 SC 的强烈表型决定，提出了使用纯培养物中的 SC 来更好地模拟临床情况的实验性应用。此外，我们还为在自体移植物上使用 ESWT 提供了论据，以提高感觉 SC 的再生能力。
