BACKGROUND: One way to overcome the genetic and molecular variations within glioblastoma is to treat each tumour on an individual basis. To facilitate this, we have developed a microfluidic culture paradigm that maintains human glioblastoma tissue ex vivo. METHODS: The assembled device, fabricated using a photolithographic process, is composed of two layers of glass bonded together to contain a tissue chamber and a network of microchannels that allow continued tissue perfusion. RESULTS: A total of 128 tissue biopsies (from 33 patients) were maintained in microfluidic devices for an average of 72 hours. Tissue viability (measured with Annexin V and propidium iodide) was 61.1% in tissue maintained on chip compared with 68.9% for fresh tissue analysed at commencement of the experiments. Other biomarkers, including lactate dehydrogenase absorbance and trypan blue exclusion, supported the viability of the tissue maintained on chip. Histological appearances remained unchanged during the tissue maintenance period, and immunohistochemical analysis of Ki67 and caspase 3 showed no significant differences when compared with fresh tissues. A trend showed that tumours associated with poorer outcomes (recurrent tumours and Isocitrate Dehydrogenase - IDH wildtype) displayed higher viability on chip than tumours linked with improved outcomes (low-grade gliomas, IDH mutants and primary tumours). conclusions: This work has demonstrated for the first time that human glioblastoma tissue can be successfully maintained within a microfluidic device and has the potential to be developed as a new platform for studying the biology of brain tumours, with the long-term aim of replacing current preclinical GBM models and facilitating personalised treatments.

背景：克服胶质母细胞瘤内遗传和分子变异的一种方法是在个体基础上治疗每个肿瘤。为了促进这一点，我们开发了一种微流控培养范例，可在体外维持人类胶质母细胞瘤组织。方法：使用光刻工艺制造的组装装置由粘合在一起的两层玻璃组成，包含一个组织室和一个允许持续组织灌注的微通道网络。结果：总共 128 个组织活检（来自 33 名患者）在微流体装置中平均维持 72 小时。保持在芯片上的组织的组织活力（用膜联蛋白 V 和碘化丙啶测量）为 61.1%，而在实验开始时分析的新鲜组织为 68.9%。其他生物标志物，包括乳酸脱氢酶吸光度和台盼蓝排除，支持保持在芯片上的组织的活力。在组织维持期间组织学外观保持不变，与新鲜组织相比，Ki67 和 caspase 3 的免疫组织化学分析显示没有显着差异。结论：这项工作首次证明了人类胶质母细胞瘤组织可以成功地保存在微流体装置中，并有可能被开发为研究脑肿瘤生物学的新平台，其长期目标是取代现有的临床前 GBM 模型和促进个性化治疗。