The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Mil Med. 2024 Aug 19;189(Suppl 3):63-66. doi: 10.1093/milmed/usae040.
Peripheral nerve injury (PNI) occurs in approximately 3% of all trauma patients and can be challenging to treat, particularly when injury is severe such as with a long-segmental gap. Although peripheral nerves can regenerate after injury, functional recovery is often insufficient, leading to deficits in the quality of life of patients with PNI. Although nerve autografts are the gold standard of care, there are several disadvantages to their use, namely a lack of autologous nerve material for repair. This has led to the pursuit of alternative treatment methods such as axon guidance channels (AGCs). Second-generation AGCs have been shown to be able to deliver growth-enhancing substrates for nerve repair directly to the injury site. Although our laboratory has had success with second-generation AGCs filled with Schwann cells (SCs), SCs have their own set of issues clinically. Because of this, we have begun to utilize SC-derived exosomes as an alternative, as they have the appropriate protein markers, associate to axons in high concentrations, and are able to improve nerve regeneration. However, it is unknown how SC-derived exosomes may react within second-generation AGCs; thus, the aim of the present study was to assess the ability of SC-derived exosomes to be loaded into a second-generation AGC and how they would distribute within it.
A total of 4 dry second-generation AGCs were loaded with SC-derived exosomes that were derived from green fluorescent protein (GFP)-labeled SCs. They were subsequently frozen and sliced before imaging.
Here, we present findings that SC-derived exosomes can be loaded into second-generation AGCs through our established loading method utilizing negative pressure and are able to survive and equally distribute along the length of the AGC.
Although only 4 second-generation AGCs were utilized, these findings indicate a potential use for SC-derived exosomes within second-generation AGCs to treat severe PNI. Future research should focus on exploring this in greater detail and in different contexts to assess the ability of SC-derived exosomes to survive at the site of injury and treat PNI.
周围神经损伤（PNI）在大约 3%的所有创伤患者中发生，治疗具有挑战性，特别是当损伤严重时，例如长节段间隙。尽管周围神经在受伤后可以再生，但功能恢复往往不足，导致 PNI 患者的生活质量下降。尽管神经自体移植物是护理的金标准，但它们的使用有几个缺点，即缺乏用于修复的自体神经材料。这导致了对替代治疗方法的追求，例如轴突导向通道（AGC）。第二代 AGC 已被证明能够将促进神经修复的生长增强基质直接递送到损伤部位。虽然我们的实验室已经成功地使用填充有施万细胞（SCs）的第二代 AGC，但SCs 在临床上存在自身问题。因此，我们已经开始将 SC 衍生的外泌体作为替代品，因为它们具有适当的蛋白质标记物，以高浓度与轴突结合，并能够改善神经再生。然而，尚不清楚 SC 衍生的外泌体在第二代 AGC 内可能会如何反应；因此，本研究的目的是评估将 SC 衍生的外泌体加载到第二代 AGC 中的能力，以及它们在其中的分布方式。
总共将 4 个干燥的第二代 AGC 加载有 SC 衍生的外泌体，这些外泌体来自绿色荧光蛋白（GFP）标记的 SC。随后将它们冷冻并切片进行成像。
在这里，我们提出了发现，SC 衍生的外泌体可以通过我们利用负压建立的加载方法加载到第二代 AGC 中，并且能够存活并沿 AGC 的长度均匀分布。
尽管仅使用了 4 个第二代 AGC，但这些发现表明 SC 衍生的外泌体在第二代 AGC 中治疗严重 PNI 具有潜在用途。未来的研究应集中在更详细和不同背景下探索这一点，以评估 SC 衍生的外泌体在损伤部位存活和治疗 PNI 的能力。
