scholarly journals Beyond 3D culture models of cancer

2015 ◽  
Vol 7 (283) ◽  
pp. 283ps9-283ps9 ◽  
Author(s):  
Kandice Tanner ◽  
Michael M. Gottesman

The mechanisms underlying the spatiotemporal evolution of tumor ecosystems present a challenge in evaluating drug efficacy. In this Perspective, we address the use of three-dimensional in vitro culture models to delineate the dynamic interplay between the tumor and the host microenvironment in an effort to attain realistic platforms for assessing pharmaceutical efficacy in patients.

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Justyna Sośniak ◽  
Jolanta Opiela

Abstract Most in vitro cell-based research is based on two-dimensional (2D) systems where growth and development take place on a flat surface, which does not reflect the natural environment of the cells. The imperfection and limitations of culture in 2D systems eventually led to the creation of three-dimensional (3D) culture models that more closely reproduce the actual conditions of physiological cell growth. Since the inception of 3D culture technology, many culture models have been developed, such as technologies of multicellular spheroids, organoids, and organs on chips in the technology of scaffolding, hydrogels, bio-printing and liquid media. In this review we will focus on the advantages and disadvantages of the 2D vs. 3D cell cultures technologies. We will also try to sum up available 3D cultures systems and materials for building 3D scaffolds.


2017 ◽  
Vol 72 ◽  
pp. S155
Author(s):  
V. Martínez-Marín ◽  
A. Redondo ◽  
V. Heredia ◽  
L. Guerra ◽  
M. Miguel-Martín ◽  
...  

2011 ◽  
Vol 301 (2) ◽  
pp. C431-C440 ◽  
Author(s):  
Hasan Erbil Abaci ◽  
Rachel Truitt ◽  
Scott Tan ◽  
Sharon Gerecht

The availability of oxygen (O2) is a critical parameter affecting vascular tube formation. In this study, we hypothesize that dissolved oxygen (DO) levels in collagen gels change during the three-dimensional (3D) culture of human umbilical vein endothelial cells (HUVECs) in atmospheric conditions and that such changes affect the kinetics of tube formation through the production of reactive oxygen species (ROS). We demonstrate a decrease in O2tension during 3D cultures of HUVECs. Noninvasive measurements of DO levels during culture under atmospheric conditions revealed a profound decrease that reached as low as 2% O2at the end of 24 h. After media replacement, DO levels rose rapidly and equilibrated at ∼15% O2, creating a reoxygenated environment. To accurately estimate DO gradients in 3D collagen gels, we developed a 3D mathematical model and determined the Michaelis-Menten parameters, Vmaxand Km, of HUVECs in collagen gels. We detected an increase in ROS levels throughout the culture period. Using diphenyliodonium to inhibit ROS production resulted in the complete inhibition of tube formation. Interference RNA studies further showed that hypoxia-inducible factors (HIFs)-1α and -2α are not involved in the formation of 3D tubes in collagen gels. We conclude that ROS affect the tubulogenesis process through HIFα-independent pathways, where the levels of ROS are influenced by the uncontrolled variations in DO levels. This study is the first demonstration of the critical and unexpected role of O2during 3D in vitro culture models of tubulogenesis in atmospheric conditions.


Biomimetics ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. 3
Author(s):  
Aya Harb ◽  
Mohammad Fakhreddine ◽  
Hassan Zaraket ◽  
Fatima A. Saleh

Respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are among the most common illnesses and a leading cause of morbidity and mortality worldwide. Due to the severe effects on health, the need of new tools to study the pathogenesis of respiratory viruses as well as to test for new antiviral drugs and vaccines is urgent. In vitro culture model systems, such as three-dimensional (3D) cultures, are emerging as a desirable approach to understand the virus host interactions and to identify novel therapeutic agents. In the first part of the article, we address the various scaffold-free and scaffold-based 3D culture models such as hydrogels, bioreactors, spheroids and 3D bioprinting as well as present their properties and advantages over conventional 2D methods. Then, we review the 3D models that have been used to study the most common respiratory viruses including influenza, parainfluenza, respiratory syncytial virus (RSV) and coronaviruses. Herein, we also explain how 3D models have been applied to understand the novel SARS-CoV-2 infectivity and to develop potential therapies.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Soran Dakhel ◽  
Wayne I. L. Davies ◽  
Justin V. Joseph ◽  
Tushar Tomar ◽  
Silvia Remeseiro ◽  
...  

Abstract Background Organ culture models have been used over the past few decades to study development and disease. The in vitro three-dimensional (3D) culture system of organoids is well known, however, these 3D systems are both costly and difficult to culture and maintain. As such, less expensive, faster and less complex methods to maintain 3D cell culture models would complement the use of organoids. Chick embryos have been used as a model to study human biology for centuries, with many fundamental discoveries as a result. These include cell type induction, cell competence, plasticity and contact inhibition, which indicates the relevance of using chick embryos when studying developmental biology and disease mechanisms. Results Here, we present an updated protocol that enables time efficient, cost effective and long-term expansion of fetal organ spheroids (FOSs) from chick embryos. Utilizing this protocol, we generated FOSs in an anchorage-independent growth pattern from seven different organs, including brain, lung, heart, liver, stomach, intestine and epidermis. These three-dimensional (3D) structures recapitulate many cellular and structural aspects of their in vivo counterpart organs and serve as a useful developmental model. In addition, we show a functional application of FOSs to analyze cell-cell interaction and cell invasion patterns as observed in cancer. Conclusion The establishment of a broad ranging and highly effective method to generate FOSs from different organs was successful in terms of the formation of healthy, proliferating 3D organ spheroids that exhibited organ-like characteristics. Potential applications of chick FOSs are their use in studies of cell-to-cell contact, cell fusion and tumor invasion under defined conditions. Future studies will reveal whether chick FOSs also can be applicable in scientific areas such as viral infections, drug screening, cancer diagnostics and/or tissue engineering.


2020 ◽  
Vol 27 (29) ◽  
pp. 4778-4788 ◽  
Author(s):  
Victoria Heredia-Soto ◽  
Andrés Redondo ◽  
José Juan Pozo Kreilinger ◽  
Virginia Martínez-Marín ◽  
Alberto Berjón ◽  
...  

Sarcomas are tumours of mesenchymal origin, which can arise in bone or soft tissues. They are rare but frequently quite aggressive and with a poor outcome. New approaches are needed to characterise these tumours and their resistance mechanisms to current therapies, responsible for tumour recurrence and treatment failure. This review is focused on the potential of three-dimensional (3D) in vitro models, including multicellular tumour spheroids (MCTS) and organoids, and the latest data about their utility for the study on important properties for tumour development. The use of spheroids as a particularly valuable alternative for compound high throughput screening (HTS) in different areas of cancer biology is also discussed, which enables the identification of new therapeutic opportunities in commonly resistant tumours.


Author(s):  
Terry Riss ◽  
O. Joseph Trask

AbstractAlong with the increased use of more physiologically relevant three-dimensional cell culture models comes the responsibility of researchers to validate new assay methods that measure events in structures that are physically larger and more complex compared to monolayers of cells. It should not be assumed that assays designed using monolayers of cells will work for cells cultured as larger three-dimensional masses. The size and barriers for penetration of molecules through the layers of cells result in a different microenvironment for the cells in the outer layer compared to the center of three-dimensional structures. Diffusion rates for nutrients and oxygen may limit metabolic activity which is often measured as a marker for cell viability. For assays that lyse cells, the penetration of reagents to achieve uniform cell lysis must be considered. For live cell fluorescent imaging assays, the diffusion of fluorescent probes and penetration of photons of light for probe excitation and fluorescent emission must be considered. This review will provide an overview of factors to consider when implementing assays to interrogate three dimensional cell culture models.


2021 ◽  
Author(s):  
Mattia Saggioro ◽  
Stefania D'Agostino ◽  
Anna Gallo ◽  
Sara Crotti ◽  
Sara D'Aronco ◽  
...  

Three-dimensional (3D) culture systems are progressively getting attention given their potential in overcoming limitations of the classical 2D in vitro systems. Among different supports for 3D cell culture, hydrogels (HGs)...


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Pirmin H. Lakner ◽  
Michael G. Monaghan ◽  
Yvonne Möller ◽  
Monilola A. Olayioye ◽  
Katja Schenke-Layland

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