Establishment of a Human Grade IV Glioma Stem Cell Line Bank

描述（申请人提供）：胶质母细胞瘤（Glioblastoma， GB）是成人最常见的原发性脑肿瘤，预后不佳，这主要归因于构成肿瘤的细胞的极端异质性，分子和遗传改变的持续进化，以及肿瘤对常规治疗的耐药性。除手术切除外，细胞毒性化合物的全身治疗是实体组织肿瘤患者的主要治疗方法。传统上，人类胶质瘤肿瘤是在体外高浓度的血清中培养的。虽然这些血清培养物可以维持很长一段时间，并且由此产生的后代在动物模型中具有致瘤性，但它们没有显示出许多在原发肿瘤中看到的决定性表型特征。最近，用于分离、扩增和研究神经干细胞的Neurosphere Assay [NSA]已应用于GB。在这些条件下，可以在规定的条件下产生GB细胞系，重要的是在培养细胞植入后产生；由此产生的肿瘤表现出典型的人GB的体内特征；概述了原发性GBMs的形态、基因型和基因表达模式，以及具有广泛的迁移和浸润能力。因此，将NSA应用于胶质瘤的研究，可以为胶质瘤生物学的研究提供一个更具生物学相关性的模型体系，并可能用于新的治疗药物的鉴定。目前还没有NSA分离的GB细胞系的商业来源，这些细胞系已经在体外和体内表型和基因组上进行了广泛的表征。在这个应用程序中，我们建议分离和储存50个这样的患者衍生系，并将它们提供给研究界。

DESCRIPTION (provided by applicant): Glioblastoma (GB) is the most common primary brain tumor in adults and has a dismal prognosis, which is attributed largely to extreme heterogeneity in the cells that make up the cancer, continual evolution of molecular and genetic alterations, and thus resistance of the tumor to conventional treatments. Beyond surgical resection, systemic treatment with cytotoxic compounds is the main treatment for patients with solid tissue tumors. Traditionally, human glioma tumors have been grown ex vivo in the presence of high concentrations of serum as adherent cultures. While these serum grown cultures can be maintained for extensive periods of time and the resulting progeny are tumorigenic in animal models, they do not display many of the defining phenotypic features that are seen in the primary tumor. Recently, application of the Neurosphere Assay [NSA], which has been used to isolate, expand and study neural stem cells, has been applied to GB. Under these conditions, GB cell lines can be generated under defined conditions and importantly following implantation of the cultured cells; the resulting tumors exhibit the classic in vivo features of human GB; recapitulating the morphology, genotype and gene expression patterns of primary GBMs, as well as having extensive migratory and infiltrative capacity. Hence, application of the NSA to the study of GB may provide a more biologically relevant model system for studying glioma biology and maybe exploited for identification of new therapeutic agents. Currently there are no commercial sources of NSA isolated GB cell lines that have been extensively characterized both phenotypically [in vitro and in vivo] and genomically. Within this application we are proposing to isolate and bank 50 such patient derived lines and make them available to the research community.