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用于体外骨髓微环境模拟以筛选白血病药物的三维多孔复合支架。

Three-dimensional porous composite scaffolds for in vitro marrow microenvironment simulation to screen leukemia drug.

机构信息

Collaborative Innovation Center for Nanomaterials & Devices, College of Physics, Qingdao University, Qingdao 266071, People's Republic of China.

出版信息

Biomed Mater. 2020 Apr 28;15(3):035016. doi: 10.1088/1748-605X/ab74e2.

DOI:10.1088/1748-605X/ab74e2
PMID:32045893
Abstract

The traditional 2D culture medium used for simulating the in vitro microenvironment for leukemia cells usually leads to 95% of the drug test results being different to the subsequent clinical results. Unlike this 2D culture, 3D scaffolds are more similar to the bone marrow microenvironment so can better simulate the drug effect on leukemia cells, which can benefit the preliminary screening of drugs for clinical use. For this purpose, the freeze-drying method was proposed for the fabrication of 3D scaffolds of graphene oxide/silk fibroin/carboxymethyl chitosan (GO/SF/CMCS). Experimental results show that these 3D scaffolds exhibit a better swelling ratio because of the embedding of GO. The improved hydrophilicity of the scaffolds brings about promoted adhesion and proliferation of leukemia cells. In contrast to the traditional 2D culture, leukemia cells in this 3D culture show stronger drug resistance, which is consistent with the previously reported clinical results. It implies that these 3D GO/SF/CMCS scaffolds can simulate well the in vivo bone marrow microenvironment, making it a promising platform for preliminary drug screening for clinical use.

摘要

传统的用于模拟白血病细胞体外微环境的 2D 培养基通常导致 95%的药物测试结果与后续的临床结果不同。与这种 2D 培养不同,3D 支架更类似于骨髓微环境,因此可以更好地模拟药物对白血病细胞的作用,这有利于临床用药的初步筛选。为此,提出了使用冷冻干燥法制备氧化石墨烯/丝素蛋白/羧甲基壳聚糖(GO/SF/CMCS)的 3D 支架。实验结果表明,由于 GO 的嵌入,这些 3D 支架具有更好的溶胀比。支架的亲水性提高促进了白血病细胞的黏附和增殖。与传统的 2D 培养相比,3D 培养中的白血病细胞表现出更强的耐药性,这与之前报道的临床结果一致。这意味着这些 3D GO/SF/CMCS 支架可以很好地模拟体内骨髓微环境,为临床用药的初步药物筛选提供了一个有前途的平台。

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Importance of Crosstalk Between Chronic Lymphocytic Leukemia Cells and the Stromal Microenvironment: Direct Contact, Soluble Factors, and Extracellular Vesicles.慢性淋巴细胞白血病细胞与基质微环境之间串扰的重要性:直接接触、可溶性因子和细胞外囊泡
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