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微工程可灌注 3D 生物打印脑胶质瘤模型,用于体内模拟肿瘤微环境。

Microengineered perfusable 3D-bioprinted glioblastoma model for in vivo mimicry of tumor microenvironment.

机构信息

Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.

Department of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.

出版信息

Sci Adv. 2021 Aug 18;7(34). doi: 10.1126/sciadv.abi9119. Print 2021 Aug.

Abstract

Many drugs show promising results in laboratory research but eventually fail clinical trials. We hypothesize that one main reason for this translational gap is that current cancer models are inadequate. Most models lack the tumor-stroma interactions, which are essential for proper representation of cancer complexed biology. Therefore, we recapitulated the tumor heterogenic microenvironment by creating fibrin glioblastoma bioink consisting of patient-derived glioblastoma cells, astrocytes, and microglia. In addition, perfusable blood vessels were created using a sacrificial bioink coated with brain pericytes and endothelial cells. We observed similar growth curves, drug response, and genetic signature of glioblastoma cells grown in our 3D-bioink platform and in orthotopic cancer mouse models as opposed to 2D culture on rigid plastic plates. Our 3D-bioprinted model could be the basis for potentially replacing cell cultures and animal models as a powerful platform for rapid, reproducible, and robust target discovery; personalized therapy screening; and drug development.

摘要

许多药物在实验室研究中显示出有前景的结果,但最终在临床试验中失败。我们假设造成这种转化差距的一个主要原因是当前的癌症模型不够充分。大多数模型缺乏肿瘤-基质相互作用,而这对于正确表现癌症复杂的生物学是至关重要的。因此,我们通过创建由患者来源的脑胶质瘤细胞、星形胶质细胞和小胶质细胞组成的纤维蛋白脑胶质瘤生物墨水,来重现肿瘤异质微环境。此外,我们使用涂有脑周细胞和内皮细胞的牺牲性生物墨水来创建可灌注的血管。我们观察到在我们的 3D 生物墨水平台中生长的脑胶质瘤细胞与在 2D 刚性塑料板培养中的细胞具有相似的生长曲线、药物反应和遗传特征,与在 2D 刚性塑料板上培养的细胞相比。我们的 3D 生物打印模型可以作为一种强大的平台,用于快速、可重复和稳健的靶点发现、个性化治疗筛选和药物开发,可能替代细胞培养和动物模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7339/8373143/9a5def012fc6/abi9119-F1.jpg

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