PDF(Pubmed)
Abstract：
Neurofibromatosis Type 1 (NF1) is a complex genetic disorder characterized by the development of benign neurofibromas, which can cause significant morbidity in affected individuals. While the molecular mechanisms underlying NF1 pathogenesis have been extensively studied, the development of effective therapeutic strategies remains a challenge. This paper presents the development and validation of a novel biomaterial testing model to enhance our understanding of NF1 pathophysiology, disease mechanisms and evaluate potential therapeutic interventions. Our long-term goal is to develop an invitro model of NF1 to evaluate drug targets. We have developed an in vitro system to test the cellular behavior of NF1 patient derived cells on electroconductive aligned nanofibrous biomaterials with electrical stimulatory cues. We hypothesized that cells cultured on electroconductive biomaterial will undergo morphological changes and variations in cell proliferation that could be further enhanced with the combination of exogenous electrical stimulation (ES). In this study, we developed electrospun Hyaluronic Acid-Carbon Nanotube (HA-CNT) nanofiber scaffolds to mimic the axon\'s topographical and bioelectrical cues that influence neurofibroma growth and development. The cellular behavior was qualitatively and quantitively analyzed through immunofluorescent stains, Alamar blue assays and ELISA assays. Schwann cells from NF1 patients appear to have lost their ability to respond to electrical stimulation in the development and regeneration range, which was seen through changes in morphology, proliferation and NGF release. Without stimulation, the conductive material enhances NF1 SC behavior. Wild-type SC respond to electrical stimulation with increased cell proliferation and NGF release. Using this system, we can better understand the interaction between axons and SC that lead to tumor formation, homeostasis and regeneration.
摘要：
1型神经纤维瘤病（NF1）是一种复杂的遗传性疾病，其特征是良性神经纤维瘤的发展。这会在受影响的个体中导致显著的发病率。虽然NF1发病机制的分子机制已被广泛研究，制定有效的治疗策略仍然是一个挑战.本文介绍了一种新型生物材料测试模型的开发和验证，以增强我们对NF1病理生理学的理解。疾病机制和评估潜在的治疗干预措施。我们的长期目标是开发NF1的体外模型来评估药物靶标。我们已经开发了一种体外系统，用于测试NF1患者来源的细胞在具有电刺激线索的导电排列纳米纤维生物材料上的细胞行为。我们假设在导电生物材料上培养的细胞将经历形态变化和细胞增殖变化，这可以通过外源性电刺激（ES）的组合进一步增强。在这项研究中,我们开发了电纺透明质酸-碳纳米管（HA-CNT）纳米纤维支架，以模拟轴突的地形和生物电线索，影响神经纤维瘤的生长和发育。通过免疫荧光染色对细胞行为进行了定性和定量分析，Alamar蓝测定和ELISA测定。来自NF1患者的施万细胞似乎在发育和再生范围内失去了对电刺激的反应能力，通过形态学的变化可以看出，增殖和NGF释放。没有刺激,导电材料增强NF1SC行为。野生型SC响应电刺激,增加细胞增殖和NGF释放。使用这个系统，我们可以更好地理解轴突和SC之间的相互作用，从而导致肿瘤的形成，稳态和再生。
