通过使用动态细胞矩阵球体组合的工程瘤肌体形态变异
Michael J Buckenmeyer1, Elizabeth A Brooks1, Madison S Taylor1
1Cancer Biomaterials Engineering Laboratory, Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702, USA.
bioRxiv : the preprint server for biology
|June 21, 2024
概括
研究人员开发了一种新的3D MatriSpheres系统,模仿瘤微环境. 这种工程外细胞矩阵 (ECM) 允许瘤细胞自我组织,影响恶性瘤并帮助精确医学.
科学领域:
- 生物医学工程 生物医学工程
- 癌症生物学 癌症生物学
- 细胞外矩阵研究研究
背景情况:
- 瘤微环境的复杂细胞外基质 (ECM) 对癌症的进展至关重要,但很难在体外复制.
- 现有的体外模型往往无法捕捉瘤细胞与其本源ECM之间的复杂相互作用.
研究的目的:
- 为了设计一个新的3D MatriSpheres系统,重复原生瘤微环境.
- 调查自组装ECM如何影响结直肠癌 (CRC) 细胞表型和恶性病变.
主要方法:
- 开发了一种使用脱细胞化小肠子粘膜 (SIS) ECM的自组装系统,用CRC细胞创建3D矩形球.
- 使用蛋白质组分析来比较SIS ECM与传统的Matrigel用于CRC同类.
- 采用单细胞RNA测序来分析3D模型中的瘤细胞的转录变化.
主要成果:
- 使用SIS ECM成功创建了3D CRC MatriSpheres,显示出与本地CRC ECM的蛋白质同质性比Matrigel更强.
- CRC细胞积极组织和集中SIS ECM,在4-5天内形成富含ECM的3D流体状区域.
- ECM组织和线索调节了与恶性瘤,脂质代谢和免疫调节相关的癌细胞程序,与体内发现一致.
结论:
- 自组装系统可以实现可扩展的,自发的工程ECM丰富的3D瘤模型.
- 这种方法刺激瘤特异性的组织形态发生,整合癌细胞和ECM复杂性.
- 3D MatriSpheres模型显示了通过更好地反映体内瘤生物学来推进精密医学的潜力.
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