增强高通量筛选3D模型:子宫颈和子宫内膜癌细胞的自动分配。

IF 2.3 4区 医学 Q3 BIOPHYSICS
Cellular and molecular bioengineering Pub Date : 2025-01-23 eCollection Date: 2025-02-01 DOI:10.1007/s12195-024-00841-y
Samantha Seymour, Ines Cadena, Mackenzie Johnson, Riya Thakkar, Molly Jenne, Iman Adem, Alyssa Almer, Rachael Frankovic, Danielle Spence, Andrea Haddadin, Kaitlin C Fogg
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引用次数: 0

摘要

目的:宫颈癌和子宫内膜癌由于其高死亡率和有限的治疗选择,对妇女保健构成重大挑战。宫颈癌和子宫内膜癌体外模型的高通量筛选(HTS)为药物再利用和拓宽患者治疗选择提供了一条有希望的途径。传统的基于二维(2D)细胞的筛选在捕捉关键的多细胞相互作用方面能力有限,而在三维(3D)多细胞组织工程模型中,这种能力得到了改进。然而,手工制作3D平台既耗时又易变。因此,本研究的目的是利用HP D100单细胞分配器制造基于3D细胞的HTS平台来分配宫颈癌和子宫内膜癌细胞。方法:我们通过调整分配方案,使其与溶液中测量的细胞大小和可接受的细胞活力和增殖的最小细胞数相一致,来评估自动分配癌细胞系的效果。我们将先前报道的宫颈癌和子宫内膜癌共培养模型修改为384孔板格式,并测量微血管长度和癌细胞侵袭。结果:直接比较了自动和手动分配细胞,揭示了分配方法之间的最小差异。这些发现表明,自动分配癌细胞对细胞行为的影响最小,可以减少体外模型制作时间。结论:通过简化制造过程,自动化配药有望提高3D体外HTS平台的效率和可扩展性,最终为癌症研究和治疗的进步做出贡献。补充信息:在线版本包含补充资料,提供地址为10.1007/s12195-024-00841-y。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Empowering High Throughput Screening of 3D Models: Automated Dispensing of Cervical and Endometrial Cancer Cells.

Purpose: Cervical and endometrial cancers pose significant challenges in women's healthcare due to their high mortality rates and limited treatment options. High throughput screening (HTS) of cervical and endometrial cancer in vitro models offers a promising avenue for drug repurposing and broadening patient treatment options. Traditional two-dimensional (2D) cell-based screenings have limited capabilities to capture crucial multicellular interactions, that are improved upon in three dimensional (3D) multicellular tissue engineered models. However, manual fabrication of the 3D platforms is both time consuming and subject to variability. Thus, the goal of this study was to utilize automated cell dispensing to fabricate 3D cell-based HTS platforms using the HP D100 Single Cell Dispenser to dispense cervical and endometrial cancer cells.

Methods: We evaluated the effects of automated dispensing of the cancer cell lines by tuning the dispensing protocol to align with cell size measured in solution and the minimum cell number for acceptable cell viability and proliferation. We modified our previously reported coculture models of cervical and endometrial cancer to be in a 384 well plate format and measured microvessel length and cancer cell invasion.

Results: Automatically and manually dispensed cells were directly compared revealing minimal differences between the dispensing methods. These findings suggest that automated dispensing of cancer cells minimally affects cell behavior and can be deployed to decrease in vitro model fabrication time.

Conclusions: By streamlining the manufacturing process, automated dispensing holds promise for enhancing efficiency and scalability of 3D in vitro HTS platforms, ultimately contributing to advancement in cancer research and treatment.

Supplementary information: The online version contains supplementary material available at 10.1007/s12195-024-00841-y.

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来源期刊
CiteScore
5.60
自引率
3.60%
发文量
30
审稿时长
>12 weeks
期刊介绍: The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.
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