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脱细胞细胞外基质在乳腺癌肿瘤模型建立和培养中的作用。

The role of decellularized cell derived extracellular matrix in the establishment and culture ofbreast cancer tumor model.

机构信息

Middle East Technical University (METU), MEMS Research and Application Center, 06530 Ankara, Turkey.

出版信息

Biomed Mater. 2024 Feb 15;19(2). doi: 10.1088/1748-605X/ad2378.

DOI:10.1088/1748-605X/ad2378
PMID:38286003
Abstract

Decades of research have shown that two-dimensional cell culture studies are insufficient for preclinical cancer diagnosis and treatment, and that cancer cells in three-dimensional (3D) culture systems have better cell-cell and cell-matrix interactions, gene expression, heterogeneity, and structural complexity that more closely resembletumors. Researchers are still optimizing 3D culturing settings for different cancers. Despite promising tumor spheroid research, tumor cell-only aggregates lack the tumor microenvironment and cannot model tumors. Here, MCF-7 breast cancer cell derived decellularized extracellular matrix (CD-dECMs) were obtained and converted into autologous, biologically active, biocompatible, and non-immunogenic hydrogels to be used as micro-environment in both organoid formation and culture. For the production of organoids, CD-dECM doping concentrations ranging from 0.1 mg mlto 1.5 mg mlwere evaluated, and the lowest concentration was found to be the most effective. For organoid culture, 8 mg mlCD-dECM, 4 mg mlrat tendon collagen type I (Col I) (4 mg ml) and a 1:1 (v/v) mixture of these two were used and the most viable and the biggest organoids were discovered in CD-dECM/Col I (1:1) group. The results show that autologous CD-dECM can replace hydrogels in tumor organoid generation and culture at low and high concentrations, respectively.

摘要

数十年的研究表明,二维细胞培养研究对于临床前癌症诊断和治疗是不够的,而在三维(3D)培养系统中的癌细胞具有更好的细胞-细胞和细胞-基质相互作用、基因表达、异质性和结构复杂性,更接近肿瘤。研究人员仍在为不同的癌症优化 3D 培养环境。尽管肿瘤球体研究前景广阔,但仅肿瘤细胞聚集缺乏肿瘤微环境,无法模拟肿瘤。在这里,获得了 MCF-7 乳腺癌细胞去细胞外基质(CD-dECM),并将其转化为自体、生物活性、生物相容和非免疫原性水凝胶,用作类器官形成和培养的微环境。为了生产类器官,评估了 CD-dECM 掺杂浓度范围为 0.1 mg ml 至 1.5 mg ml,发现最低浓度最有效。对于类器官培养,使用了 8 mg ml CD-dECM、4 mg ml 大鼠肌腱胶原 I(Col I)(4 mg ml)和这两种物质的 1:1(v/v)混合物,在 CD-dECM/Col I(1:1)组中发现了最有活力和最大的类器官。结果表明,自体 CD-dECM 可以分别在低浓度和高浓度下替代水凝胶用于肿瘤类器官的生成和培养。

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