Rota Christopher M, Brown Alexander T, Addleson Emily, Ives Clara, Trumper Ella, Pelton Kristine, Teh Wei Pin, Schniederjan Matthew J, Castellino Robert Craig, Buhrlage Sara, Lauffenburger Douglas A, Ligon Keith L, Griffith Linda G, Segal Rosalind A
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Neurooncol Adv. 2022 Apr 13;4(1):vdac049. doi: 10.1093/noajnl/vdac049. eCollection 2022 Jan-Dec.
Pediatric gliomas comprise a diverse set of brain tumor entities that have substantial long-term ramifications for patient survival and quality of life. However, the study of these tumors is currently limited due to a lack of authentic models. Additionally, many aspects of pediatric brain tumor biology, such as tumor cell invasiveness, have been difficult to study with currently available tools. To address these issues, we developed a synthetic extracellular matrix (sECM)-based culture system to grow and study primary pediatric brain tumor cells.
We developed a brain-like sECM material as a supportive scaffold for the culture of primary, patient-derived pediatric glioma cells and established patient-derived cell lines. Primary juvenile brainstem-derived murine astrocytes were used as a feeder layer to support the growth of primary human tumor cells.
We found that our culture system facilitated the proliferation of various primary pediatric brain tumors, including low-grade gliomas, and enabled ex vivo testing of investigational therapeutics. Additionally, we found that tuning this sECM material allowed us to assess high-grade pediatric glioma cell invasion and evaluate therapeutic interventions targeting invasive behavior.
Our sECM culture platform provides a multipurpose tool for pediatric brain tumor researchers that enables both a wide breadth of biological assays and the cultivation of diverse tumor types.
小儿胶质瘤是一组多样的脑肿瘤实体,对患者的生存和生活质量有重大的长期影响。然而,由于缺乏可靠的模型,目前对这些肿瘤的研究受到限制。此外,小儿脑肿瘤生物学的许多方面,如肿瘤细胞的侵袭性,使用现有的工具很难进行研究。为了解决这些问题,我们开发了一种基于合成细胞外基质(sECM)的培养系统,用于培养和研究原发性小儿脑肿瘤细胞。
我们开发了一种类似脑的sECM材料,作为原发性、患者来源的小儿胶质瘤细胞培养的支持支架,并建立了患者来源的细胞系。原发性幼年脑干来源的小鼠星形胶质细胞用作饲养层,以支持原发性人类肿瘤细胞的生长。
我们发现我们的培养系统促进了各种原发性小儿脑肿瘤的增殖,包括低级别胶质瘤,并能够对研究性治疗进行体外测试。此外,我们发现调整这种sECM材料使我们能够评估高级别小儿胶质瘤细胞的侵袭,并评估针对侵袭行为的治疗干预措施。
我们的sECM培养平台为小儿脑肿瘤研究人员提供了一种多功能工具,可以进行广泛的生物学检测,并培养多种肿瘤类型。