Three-Dimensional Cell Cultures in Toxicology

Pampaloni, Francesco; Stelzer, Ernst H. K.

doi:10.5661/bger-26-117

Cited by 72 publications

(56 citation statements)

References 91 publications

(86 reference statements)

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“…Traditionally, in vitro research has been conducted using 2D cell cultures. However, conventional 2D cell culture where cells are cultured on flat, rigid plastic substrates does not reproduce the tissue architecture in vivo , and do not forecast organ-specific toxicity [4,5]. This is because real tissues have a 3D geometry, gel-like stiffness, and complex organisation of extracellular matrix (ECM).…”

Section: Introductionmentioning

confidence: 99%

Development of In Vitro 3D TissueFlex® Islet Model for Diabetic Drug Efficacy Testing

Sun

Zhang

et al. 2013

PLoS ONE

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Increasing individuals diagnosed with type II diabetes pose a strong demand for the development of more effective anti-diabetic drugs. However, expensive, ethically controversial animal-based screening for anti-diabetic compounds is not always predictive of the human response. The use of in vitro cell-based models in research presents obviously ethical and cost advantages over in vivo models. This study was to develop an in vitro three-dimensional (3D) perfused culture model of islets (Islet TF) for maintaining viability and functionality longer for diabetic drug efficacy tests. Briefly fresh isolated rat islets were encapsulated in ultrapure alginate and the encapsulated islets were cultured in TissueFlex®, a multiple, parallel perfused microbioreactor system for 7 days. The encapsulated islets cultured statically in cell culture plates (3D static) and islets cultured in suspension (2D) were used as the comparisons. In this study we demonstrate for the first time that Islet TF model can maintain the in vitro islet viability, and more importantly, the elevated functionality in terms of insulin release and dynamic responses over a 7-day culture period. The Islet TF displays a high sensitivity in responding to drugs and drug dosages over conventional 2D and 3D static models. Actual drug administration in clinics could be simulated using the developed Islet TF model, and the patterns of insulin release response to the tested drugs were in agreement with the data obtained in vivo. Islet TF could be a more predictive in vitro model for routine short- and long-term anti-diabetic drug efficacy testing.

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Section: Introductionmentioning

confidence: 99%

Development of In Vitro 3D TissueFlex® Islet Model for Diabetic Drug Efficacy Testing

Sun

Zhang

et al. 2013

PLoS ONE

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“…Matrigel is derived from the Engelbreth-Holm-Swarm mouse carcinoma and can be reconstituted as a 3D gel under physiological pH and temperature [42, 43]. For 3D cultures, Matrigel was poured onto tissue culture plates to a depth of approximately 0.2 mm followed by polymerization for 1 hour at 37°C before placement of cells on the Matrigel surface.…”

Section: Methodsmentioning

confidence: 99%

Increased Resistance of Breast, Prostate, and Embryonic Carcinoma Cells against Herpes Simplex Virus in Three-Dimensional Cultures

et al. 2013

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In previous studies we found that uveal melanoma cells grown in extracellular matrix (ECM)-containing three-dimensional (3D) cultures have increased resistance against herpes simplex virus type 1 (HSV-1)-mediated destruction relative to cells cultured without ECM. Using additional tumor cell types including MB-231 human breast cancer cells, PC-3 human prostate cancer cells, and P19 mouse embryonal carcinoma cells, we show here that tumor cell lines other than melanoma are also more resistant to HSV-1-mediated destruction in 3D cultures than cells grown in 2D. We also demonstrate here that one mechanism responsible for the increased resistance of tumor cells to HSV-1 infection in 3D cultures is an ECM-mediated inhibition of virus replication following virus entry into cells. These findings confirm and extend previous observations related to the role of the ECM in tumor resistance against HSV-1 and may lead to improved strategies of oncolytic virotherapy.

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“…This paradigm is of particular significance in drug screening applications, in which in vitro culture models must adequately represent cells in vivo , in order to generate clinically translatable results. 56, 57 Several recent reviews emphasize the importance and challenges associated with 3D culture systems. 58, 59 Such challenges include the increased cost and operational complexity of using 3D biomaterials, the difficulties in extracting biological samples for analysis, and the experimental challenges associated with decoupling confounding biological effects.…”

Section: Biological Applications Of Fracture Based Micro- and Nanomentioning

confidence: 99%

Fracture-based micro- and nanofabrication for biological applications

et al. 2014

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While fracture is generally considered to be undesirable in various manufacturing processes, delicate control of fracture can be successfully implemented to generate structures at micro/nano length scales. Fracture-based fabrication techniques can serve as a template-free manufacturing method, and enables highly-ordered patterns or fluidic channels to be formed over large areas in a simple and cost-effective manner. Such technologies can be leveraged to address biologically-relevant problems, such as in the analysis of biomolecules or in the design of culture systems that imitate the cellular or molecular environment. This mini review provides an overview of current fracture-guided fabrication techniques and their biological applications. We first survey the mechanical principles of fracture-based approaches. Then we describe biological applications at the cellular and molecular levels. Finally, we discuss unique advantages of the different system for biological studies.

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Three-Dimensional Cell Cultures in Toxicology

Cited by 72 publications

References 91 publications

Development of In Vitro 3D TissueFlex® Islet Model for Diabetic Drug Efficacy Testing

Development of In Vitro 3D TissueFlex® Islet Model for Diabetic Drug Efficacy Testing

Increased Resistance of Breast, Prostate, and Embryonic Carcinoma Cells against Herpes Simplex Virus in Three-Dimensional Cultures

Fracture-based micro- and nanofabrication for biological applications

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