Abstract：
BACKGROUND: Our goal was to develop a 3D tumor slice model, replicating the individual tumor microenvironment and for individual pharmaceutical testing in vestibular schwannomas with and without relation to NF2.
METHODS: Tissue samples from 16 VS patients (14 sporadic, 2 NF2-related) were prospectively analyzed. Slices of 350 µm thickness were cultured in vitro, and the 3D tumor slice model underwent thorough evaluation for culturing time, microenvironment characteristics, morphology, apoptosis, and proliferation rates. Common drugs - Lapatinib (10 µM), Nilotinib (20 µM), and Bevacizumab (10 µg/ml) - known for their responses in VS were used for treatment. Treatment responses were assessed using CC3 as an apoptosis marker and Ki67 as a proliferation marker. Standard 2D cell culture models of the same tumors served as controls.
RESULTS: The 3D tumor slice model accurately mimicked VS ex vivo, maintaining stability for three months. Cell count within the model was approximately tenfold higher than in standard cell culture, and the tumor microenvironment remained stable for 46 days. Pharmacological testing was feasible for up to three weeks, revealing interindividual differences in treatment response to Lapatinib and intraindividual variability in response to Lapatinib and Nilotinib. The observed effects were less pronounced in tumor slices than in standard cell culture, indicating the model\'s proximity to in vivo tumor biology and enhanced realism. Bevacizumab had limited impact in both models.
CONCLUSIONS: This study introduces a 3D tumor slice model for sporadic and NF2-related VS, demonstrating stability for up to 3 months, replication of the schwannoma microenvironment, and utility for individualized pharmacological testing.
METHODS: Tissue samples from 16 VS patients (14 sporadic, 2 NF2-related) were prospectively analyzed. Slices of 350 µm thickness were cultured in vitro, and the 3D tumor slice model underwent thorough evaluation for culturing time, microenvironment characteristics, morphology, apoptosis, and proliferation rates. Common drugs - Lapatinib (10 µM), Nilotinib (20 µM), and Bevacizumab (10 µg/ml) - known for their responses in VS were used for treatment. Treatment responses were assessed using CC3 as an apoptosis marker and Ki67 as a proliferation marker. Standard 2D cell culture models of the same tumors served as controls.
RESULTS: The 3D tumor slice model accurately mimicked VS ex vivo, maintaining stability for three months. Cell count within the model was approximately tenfold higher than in standard cell culture, and the tumor microenvironment remained stable for 46 days. Pharmacological testing was feasible for up to three weeks, revealing interindividual differences in treatment response to Lapatinib and intraindividual variability in response to Lapatinib and Nilotinib. The observed effects were less pronounced in tumor slices than in standard cell culture, indicating the model\'s proximity to in vivo tumor biology and enhanced realism. Bevacizumab had limited impact in both models.
CONCLUSIONS: This study introduces a 3D tumor slice model for sporadic and NF2-related VS, demonstrating stability for up to 3 months, replication of the schwannoma microenvironment, and utility for individualized pharmacological testing.
摘要：
背景：为了开发3D肿瘤切片模型，复制单个肿瘤微环境，并在与NF2无关的前庭神经鞘瘤中进行单独的药物测试。
方法：来自16例VS患者的组织样本（14例散发性，2NF2相关)进行了前瞻性分析。350μm厚的切片在体外培养，并对3D肿瘤切片模型进行了全面的培养时间评估，微环境特征，形态学,凋亡，和扩散速率。常见药物-拉帕替尼（10µM），尼洛替尼（20µM），和贝伐单抗（10µg/ml）-已知在VS中的反应被用于治疗。使用CC3作为凋亡标志物和Ki67作为增殖标志物来评估治疗反应。相同肿瘤的标准2D细胞培养模型用作对照。
结果：3D肿瘤切片模型准确地模仿了离体VS，保持稳定三个月。模型中的细胞计数比标准细胞培养物高约10倍，肿瘤微环境稳定46天。药理学测试是可行的长达三周，揭示对拉帕替尼治疗反应的个体差异和对拉帕替尼和尼洛替尼反应的个体差异。在肿瘤切片中观察到的效果不如在标准细胞培养物中明显，表明该模型与体内肿瘤生物学接近，增强了现实性。贝伐单抗在两种模型中的影响有限。
结论：结论：本研究引入了散发性和NF2相关VS的3D肿瘤切片模型，显示稳定性长达3个月，神经鞘瘤微环境的复制，和个体化药理试验的实用性。
方法：来自16例VS患者的组织样本（14例散发性，2NF2相关)进行了前瞻性分析。350μm厚的切片在体外培养，并对3D肿瘤切片模型进行了全面的培养时间评估，微环境特征，形态学,凋亡，和扩散速率。常见药物-拉帕替尼（10µM），尼洛替尼（20µM），和贝伐单抗（10µg/ml）-已知在VS中的反应被用于治疗。使用CC3作为凋亡标志物和Ki67作为增殖标志物来评估治疗反应。相同肿瘤的标准2D细胞培养模型用作对照。
结果：3D肿瘤切片模型准确地模仿了离体VS，保持稳定三个月。模型中的细胞计数比标准细胞培养物高约10倍，肿瘤微环境稳定46天。药理学测试是可行的长达三周，揭示对拉帕替尼治疗反应的个体差异和对拉帕替尼和尼洛替尼反应的个体差异。在肿瘤切片中观察到的效果不如在标准细胞培养物中明显，表明该模型与体内肿瘤生物学接近，增强了现实性。贝伐单抗在两种模型中的影响有限。
结论：结论：本研究引入了散发性和NF2相关VS的3D肿瘤切片模型，显示稳定性长达3个月，神经鞘瘤微环境的复制，和个体化药理试验的实用性。
