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Toxicity and Cellular Uptake of Gold Nanoparticles: What We Have Learned So Far *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Alaaldin M. Alkilany, Catherine J. Murphy
In vitro three-dimensional (3D) cell culture models have been used as a bridge between the in vitro two-dimensional (2D) plated cell culture and the in vivo models (Griffith and Swartz 2006; Yamada and Cukierman 2007). In this context, Lee et al. compared the toxicity of gold nanoparticles in both 2D and 3D cell culture constructs. They used hydrogel inverted colloidal crystals as a cell growth substrate and human hepatocarcinoma cells to construct the 3D cell culture environment. They found that toxicity of both citrate (anionic)- and CTAB (cationic)-capped gold nanoparticles were significantly reduced in the 3D environment compared to 2D (Lee et al. 2009). These results point out that in vitro studies alone are not adequate to assess toxicity of nanoparticles.
A Strategy for Regeneration of Three-Dimensional (3D) Microtissues in Microcapsules: Aerosol Atomization Technique
Published in Naznin Sultana, Sanchita Bandyopadhyay-Ghosh, Chin Fhong Soon, Tissue Engineering Strategies for Organ Regeneration, 2020
Chin Fhong Soon, Wai Yean Leong, Kian Sek Tee, Mohd Khairul Ahmad, Nafarizal Nayan
Culturing monolayers of cells in plastic dishes is routinely performed in life sciences and cell biological studies. Currently, scientific committee has begun to realize the many limitations of monolayer or two-dimensional (2D) culture model (Antoni et al. 2015, Souza et al. 2010). 2D cell model is missing accurate representation of physiological origins in terms of the proliferation, differentiation, gene and protein expression, functionality and morphology of cells (Edmondson et al. 2014). Contrarily, the three-dimensional (3D) cell culture creates extracellular matrix where cells are permitted to grow or interact with its surroundings. 3D cell culture regenerates biological relevant tissue model that restores specific cellular activities, signaling molecules and morphological structures similar to those in vivo (Kunz-Schughart et al. 2004). The cell interactions, responses and organization occurring within a 3D context demonstrated more native like and the severe limitations of 2D culture (Edmondson et al. 2014, Soon et al. 2016). 3D cell culture is part of the effort in regenerative medicine or biotechnology to recreate living and functional tissues in vitro, in which they are needed for replacement of damaged tissues (Kang et al. 2014), cancer research, application in tissue engineering (Stevens et al. 2004), pharmacological testing and stem cell research (Sugiura et al. 2005). Microencapsulation is an intensive research area to create cell and tissue model for rehabilitation of functional tissues (Zhao et al. 2017) and therapeutics purpose (da Rocha et al. 2014, Shin et al. 2013).
Body-on-a-Chip for Pharmacology and Toxicology
Published in Brian J. Lukey, James A. Romano, Salem Harry, Chemical Warfare Agents, 2019
Anthony Atala, Mahesh Devarasetty, Steven. D. Forsythe, Russell. M. Dorsey, Harry Salem, Thomas. D. Shupe, Aleksander Skardal, Shay Soker
3-D cell culture can be separated into two major types: scaffold-based technologies and scaffold-free technologies. Scaffold-based technologies rely on a premade substrate material for the attachment of cells: for example, cells can be suspended in hydrogel solutions of collagen or hyaluronic acid, which allow the attachment and reorganization of cells. Additionally, cells can be seeded onto the ECM of a previously decellularized tissue (Baptista et al., 2013; Ruedinger et al., 2015). Scaffolds can also be constructed from synthetic materials such as polycaprolactone (PCL) or poly(lactic-co-glycolic acid) (PLGA), which are biocompatible and biodegradable polymers. Polymeric scaffolds can be constructed in a range of sizes, shapes, and stiffnesses using 3-D extrusion-based printers, electrospinning, or basic molding techniques (Gentile et al., 2014; Place et al., 2009).
Three-dimensional (3D) cell culture studies: a review of the field of toxicology
Published in Drug and Chemical Toxicology, 2023
Seda İpek, Aylin Üstündağ, Benay Can Eke
Cells respond to specific signals and cues in their 3D environment, resulting in cell proliferation, differentiation, and function in the body (Knight and Przyborski 2015). This process depends on interactions between cells and extracellular matrix (ECM), and ingredients of the ECM as well (Saydé et al.2021). There are diverse methods available for 3D cell culture techniques. However, no technology can satisfy the requirements of all 3D cell cultures, and therefore users must choose the model that best meets their needs (Knight and Przyborski 2015). A 3D system needs to hold a few key characteristics, such as retaining the natural shape of the cell and allowing heterogeneous contact between the surface of the cell and the medium. In addition, it should be possible to observe high cell viability and proliferation in 3D systems (Saydé et al.2021). 3D culture techniques can be categorized into two main groups; scaffold-based and scaffold-free methods (Souza et al.2016). However, organoids can be generated with or without a scaffold (Baert et al.2017), and thus we separated the cell culture techniques into three groups by mentioning organoids separately from the other techniques.
Upregulation of microRNA-155 Enhanced Migration and Function of Dendritic Cells in Three-dimensional Breast Cancer Microenvironment
Published in Immunological Investigations, 2021
Pengxiang Yang, Xingjian Cao, Huilong Cai, Xiang Chen, Yihua Zhu, Yue Yang, Weiwei An, Jing Jie
DCs often display an immature status due to weak immunogenicity and the immune-suppressive tumor microenvironment, resulting in tumor escape (Kohnepoushi et al. 2019; Sabado and Bhardwaj 2015; Son et al. 2013). To increase confidence in DCs immunotherapy and to demonstrate its great clinical value, we explored whether cell function could be enhanced by a strategy that involves manipulating the intrinsic regulatory function of miR-155 (Gardner and Ruffell 2016; Palucka and Banchereau 2013). Three-dimensional cell culture is now of increasing interest in research that attempts to predict the pharmacodynamics and toxicity of drugs and the effects of vaccine candidates (Markey et al. 2017). Because 3D cell culture is superior to standard 2D cell culture conditions, 3D cell culture may better mimic complex physiological phenomena in vivo (Sprague et al. 2014; Yang et al. 2018). Recently, hydrogel matrices were used as the mechanical support of immune cells for further research (Groell et al. 2018). In this study, we developed a 3D cell culture model that encapsulates DCs in a simple Matrigel scaffold that mimics the mechanical properties of tissues. Matrigel is a basement membrane-derived preparation extracted from mouse sarcoma tumors that closely mimics the immunosuppressive tumor microenvironment in vivo (Caliari and Burdick 2016). The viability and function of DCs was studied in this model, which was shown to be applicable and effective.
Using 3D in vitro cell culture models in anti-cancer drug discovery
Published in Expert Opinion on Drug Discovery, 2021
Undoubtedly and rightfully, 3D cell cultures are making their way into mainstream cancer drug discovery. While in the past, cell-based high-throughput drug discovery relied on chemical screens of well-characterized 2D cultures in plastic multi-well dishes, the realization that monolayer cultures omit important aspects that determine a cancer cell’s behavior and therapeutic response, namely the bidirectional interactions between cancer cells and their immediate environment, has emphasized the need for more physiologically relevant cell culture systems. Simply by design, 3D cultures can replicate cell-cell and cell-ECM interactions found in tumor tissue and thus, lend themselves to be developed as drug discovery platforms with higher predictive value and higher success rate of bench-to-bed translation. This is particularly true for scaffold-based 3D cell culture technologies that can mimic complex microenvironments. Applications for anchorage-independent spheroid cell aggregates have to be selected carefully and targeted to specific needs, making their use in 3D drug discovery somewhat more limited. However, until scaffold-based 3D cultures become a staple in mainstream drug development, technical and biological challenges remain to be overcome [5–7,9,74,93]. Thus, when developing new 3D cell culture technologies it will be advantageous to consider current limitations to 3D cell cultures and address these drawbacks right in the outset of the new design.