scholarly journals Three-Dimensional Cell Cultures in Drug Discovery and Development

2017 ◽  
Vol 22 (5) ◽  
pp. 456-472 ◽  
Author(s):  
Ye Fang ◽  
Richard M. Eglen

The past decades have witnessed significant efforts toward the development of three-dimensional (3D) cell cultures as systems that better mimic in vivo physiology. Today, 3D cell cultures are emerging, not only as a new tool in early drug discovery but also as potential therapeutics to treat disease. In this review, we assess leading 3D cell culture technologies and their impact on drug discovery, including spheroids, organoids, scaffolds, hydrogels, organs-on-chips, and 3D bioprinting. We also discuss the implementation of these technologies in compound identification, screening, and development, ranging from disease modeling to assessment of efficacy and safety profiles.

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 249-253
Author(s):  
Marta Bochynska-Czyz ◽  
Patrycja Redkiewicz ◽  
Hanna Kozlowska ◽  
Joanna Matalinska ◽  
Marek Konop ◽  
...  

AbstractThree-dimensional (3D) cell cultures were created with the use of fur keratin associated proteins (F-KAPs) as scaffolds. The procedure of preparation F-KAP involves combinations of chemical activation and enzymatic digestion. The best result in porosity and heterogeneity of F-KAP surface was received during pepsin digestion. The F-KAP had a stable structure, no changes were observed after heat treatment, shaking and washing. The 0.15-0.5 mm fraction had positive effect for formation of 3D scaffolds and cell culturing. Living rat mesenchymal cells on the F-KAP with no abnormal morphology were observed by SEM during 32 days of cell culturing.


Chemosensors ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 6 ◽  
Author(s):  
Georgia Paivana ◽  
Theofylaktos Apostolou ◽  
Sophie Mavrikou ◽  
Dimitris Barmpakos ◽  
Grigoris Kaltsas ◽  
...  

In this work, the assessment of the interactions of a bioactive substance applied to immobilized cells in either a two-dimensional (2D) or three-dimensional (3D) arrangement mimicking in vivo tissue conditions is presented. In particular, dopamine (DA) was selected as a stimulant for the implementation of an impedance analysis with a specific type of neural cells (murine neuroblastoma). The aim of this study was the extraction of calibration curves at various frequencies with different known dopamine concentrations for the description of the behavior of dopamine applied to 2D and 3D cell cultures. The results present the evaluation of the mean impedance value for each immobilization technique in each frequency. The differential responses showed the importance of the impedance when frequency is applied in both 2D and 3D immobilization cases. More specifically, in 2D immobilization matrix impedance shows higher values in comparison with the 3D cell culture. Additionally, in the 3D case, the impedance decreases with increasing concentration, while in the 2D case, an opposite behavior was observed.


2020 ◽  
Vol 21 (18) ◽  
pp. 6806 ◽  
Author(s):  
Fabrizio Fontana ◽  
Michela Raimondi ◽  
Monica Marzagalli ◽  
Michele Sommariva ◽  
Nicoletta Gagliano ◽  
...  

In the last decade, three-dimensional (3D) cell culture technology has gained a lot of interest due to its ability to better recapitulate the in vivo organization and microenvironment of in vitro cultured cancer cells. In particular, 3D tumor models have demonstrated several different characteristics compared with traditional two-dimensional (2D) cultures and have provided an interesting link between the latter and animal experiments. Indeed, 3D cell cultures represent a useful platform for the identification of the biological features of cancer cells as well as for the screening of novel antitumor agents. The present review is aimed at summarizing the most common 3D cell culture methods and applications, with a focus on prostate cancer modeling and drug discovery.


2020 ◽  
Vol 25 (3) ◽  
pp. 234-246
Author(s):  
Charles McRae White ◽  
Mark A. Haidekker ◽  
William S. Kisaalita

New insights into the biomechanical properties of cells are revealing the importance of these properties and how they relate to underlying molecular, architectural, and behavioral changes associated with cell state and disease processes. However, the current understanding of how these in vitro biomechanical properties are associated with in vivo processes has been developed based on the traditional monolayer (two-dimensional [2D]) cell culture, which traditionally has not translated well to the three-dimensional (3D) cell culture and in vivo function. Many gold standard methods and tools used to observe the biomechanical properties of 2D cell cultures cannot be used with 3D cell cultures. Fluorescent molecules can respond to external factors almost instantaneously and require relatively low-cost instrumentation. In this review, we provide the background on fluorescent molecular rotors, which are attractive tools due to the relationship of their emission quantum yield with environmental microviscosity. We make the case for their use in both 2D and 3D cell cultures and speculate on their fundamental and practical applications in cell biology.


Author(s):  
Loh Teng Hern Tan ◽  
Liang Ee Low ◽  
Siah Ying Tang ◽  
Wei Hsum Yap ◽  
Lay Hong Chuah ◽  
...  

Three-dimensional cell culture methods revolutionize the field of anticancer drug discovery, forming an important link-bridge between conventional in vitro and in vivo models and conferring significant clinical and biological relevant data. The current work presents an affordable yet reproducible method of generating homogenous 3D tumor spheroids. Also, a new open source software is adapted to perform an automated image analysis of 3D tumor spheroids and subsequently generate a list of morphological parameters of which could be utilized to determine the response of these spheroids toward treatments. Our data showed that this work could serve as a reliable 3D cell culture platform for preclinical cytotoxicity testing of natural products prior to the expensive and time-consuming animal models


2012 ◽  
Author(s):  
Frances A. Brightman ◽  
Eric Fernandez ◽  
David Orrell ◽  
David Fell ◽  
Christophe Chassagnole

2018 ◽  
Vol 24 (1) ◽  
pp. 3-17 ◽  
Author(s):  
Richard M. Eglen ◽  
Terry Reisine

Human-induced pluripotent stem cells (HiPSCs), and new technologies to culture them into functional cell types and tissues, are now aiding drug discovery. Patient-derived HiPSCs can provide disease models that are more clinically relevant and so more predictive than the currently available animal-derived or tumor cell-derived cells. These cells, consequently, exhibit disease phenotypes close to the human pathology, particularly when cultured under conditions that allow them to recapitulate the tissue architecture in three-dimensional (3D) systems. A key feature of HiPSCs is that they can be cultured under conditions that favor formation of multicellular spheroids or organoids. By culturing and differentiating in systems mimicking the human tissue in vivo, the HiPSC microenvironment further reflects patient in vivo physiology, pathophysiology, and ultimately pharmacological responsiveness. We assess the rationale for using HiPSCs in several phases of preclinical drug discovery, specifically in disease modeling, target identification, and lead optimization. We also discuss the growing use of HiPSCs in compound lead optimization, particularly in profiling compounds for their potential metabolic liability and off-target toxicities. Collectively, we contend that both approaches, HiPSCs and 3D cell culture, when used in concert, have exciting potential for the development of novel medicines.


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