scholarly journals Novel Nanomaterials Enable Biomimetic Models of the Tumor Microenvironment

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Marshall Hunter Joyce ◽  
Shane Allen ◽  
Laura Suggs ◽  
Amy Brock

In the complex tumor microenvironment, chemical and mechanical signals from tumor cells, stromal cells, and the surrounding extracellular matrix influence all aspects of disease progression and response to treatment. Modeling the physical properties of the tumor microenvironment has been a significant effort in the biomaterials field. One challenge has been the difficulty in altering the mechanical properties of the extracellular matrix without simultaneously impacting other factors that influence cell behavior. The development of novel materials based on nanotechnology has enabled recent innovations in tumor cell culture models. Here, we review the various approaches by which the tumor cell microenvironment has been engineered using natural and synthetic gels. We describe new studies that rely on the unique temporal and spatial control afforded by nanomaterials to produce culture platforms that mimic dynamic changes in tumor matrix mechanics. In addition, we look at the frontier of nanomaterial-hydrogel composites to review new approaches for perturbation of mechanochemical control in the tumor microenvironment.

Author(s):  
А.Н. Чернов ◽  
Е.П. Баранцевич ◽  
Э.С. Галимова ◽  
М.М. Галагудза

Современный эффективный скрининг новых противоопухолевых химиопрепаратов и биологических препаратов на доклиническом этапе невозможен без применения моделей культур опухолевых клеток. К таким моделям относят первичные культуры клеток и клеточные линии опухолей человека, культивируемые в двумерной (2D) и трехмерной (3D) системах. В обзоре обсуждаются различные аспекты применения моделей клеточных культур неоплазий человека, их актуальность в исследованиях противоопухолевой эффективности препаратов. Current effective preclinical screening of new anticancer chemotherapies and biological medicines requires cancer cell culture models. Such models include primary cell cultures and human tumor cell lines cultured in two-dimensional (2D) and three-dimensional (3D) systems. This review discussed different aspects of using human tumor cell culture models and their relevance for studying efficacy of antitumor drugs.


Biomaterials ◽  
2017 ◽  
Vol 116 ◽  
pp. 118-129 ◽  
Author(s):  
Mónica Romero-López ◽  
Andrew L. Trinh ◽  
Agua Sobrino ◽  
Michaela M.S. Hatch ◽  
Mark T. Keating ◽  
...  

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 190
Author(s):  
Mélanie A. G. Barbosa ◽  
Cristina P. R. Xavier ◽  
Rúben F. Pereira ◽  
Vilma Petrikaitė ◽  
M. Helena Vasconcelos

Today, innovative three-dimensional (3D) cell culture models have been proposed as viable and biomimetic alternatives for initial drug screening, allowing the improvement of the efficiency of drug development. These models are gaining popularity, given their ability to reproduce key aspects of the tumor microenvironment, concerning the 3D tumor architecture as well as the interactions of tumor cells with the extracellular matrix and surrounding non-tumor cells. The development of accurate 3D models may become beneficial to decrease the use of laboratory animals in scientific research, in accordance with the European Union’s regulation on the 3R rule (Replacement, Reduction, Refinement). This review focuses on the impact of 3D cell culture models on cancer research, discussing their advantages, limitations, and compatibility with high-throughput screenings and automated systems. An insight is also given on the adequacy of the available readouts for the interpretation of the data obtained from the 3D cell culture models. Importantly, we also emphasize the need for the incorporation of additional and complementary microenvironment elements on the design of 3D cell culture models, towards improved predictive value of drug efficacy.


Micromachines ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 382 ◽  
Author(s):  
Valentina Palacio-Castañeda ◽  
Lucas Kooijman ◽  
Bastien Venzac ◽  
Wouter Verdurmen ◽  
Séverine Le Gac

Hypoxia switches the metabolism of tumor cells and induces drug resistance. Currently, no therapeutic exists that effectively and specifically targets hypoxic cells in tumors. Development of such therapeutics critically depends on the availability of in vitro models that accurately recapitulate hypoxia as found in the tumor microenvironment. Here, we report on the design and validation of an easy-to-fabricate tumor-on-a-chip microfluidic platform that robustly emulates the hypoxic tumor microenvironment. The tumor-on-a-chip model consists of a central chamber for 3D tumor cell culture and two side channels for medium perfusion. The microfluidic device is fabricated from polydimethylsiloxane (PDMS), and oxygen diffusion in the device is blocked by an embedded sheet of polymethyl methacrylate (PMMA). Hypoxia was confirmed using oxygen-sensitive probes and the effect on the 3D tumor cell culture investigated by a pH-sensitive dual-labeled fluorescent dextran and a fluorescently labeled glucose analogue. In contrast to control devices without PMMA, PMMA-containing devices gave rise to decreases in oxygen and pH levels as well as an increased consumption of glucose after two days of culture, indicating a rapid metabolic switch of the tumor cells under hypoxic conditions towards increased glycolysis. This platform will open new avenues for testing anti-cancer therapies targeting hypoxic areas.


2016 ◽  
Vol 4 (4) ◽  
pp. 610-613 ◽  
Author(s):  
Forrest M. Kievit ◽  
Kui Wang ◽  
Ariane E. Erickson ◽  
Sheeny K. Lan Levengood ◽  
Richard G. Ellenbogen ◽  
...  

Investigate the effects of various components of the glioblastoma microenvironment including extracellular matrix and stromal cells on tumor cell stem-like state.


2020 ◽  
Vol 15 (03) ◽  
pp. 131-141
Author(s):  
Yu Ling Huang ◽  
Carina Shiau ◽  
Cindy Wu ◽  
Jeffrey E. Segall ◽  
Mingming Wu

Tumor invasion, the process by which tumor cells break away from their primary tumor and gain access to vascular systems, is an important step in cancer metastasis. Most current 3D tumor invasion assays consisted of a single tumor cell embedded within an extracellular matrix (ECM). These assays taught us much of what we know today on how key biophysical (e.g., ECM stiffness) and biochemical (e.g., cytokine gradients) parameters within the tumor microenvironment guided and regulated tumor invasion. One limitation of the single tumor cell invasion assays was that it did not account for cell–cell adhesion within the tumor. In this paper, we developed a micrometer scale 3D co-culture spheroid invasion assay that recapitulated physiologically realistic tumor microenvironment and was compatible with microscopic imaging. Micrometer scale co-culture spheroids (1:1 ratio of metastatic breast cancer MDA-MB-231 and non-tumorigenic epithelial MCF-10A cells) were made using an array of microwells, and then were embedded within a collagen matrix in a microfluidic platform. Real time imaging of tumor spheroid invasion revealed that the spatial distribution of the two cell types within the tumor spheroid critically regulated tumor invasion. This work linked tumor architecture with tumor invasion and highlighted the importance of the biophysical cues within the bulk of the tumor in tumor invasion.


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