scholarly journals A reliable and affordable 3D tumor spheroid model for natural product drug discovery: A case study of curcumin

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

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Laurence Finot ◽  
Eric Chanat ◽  
Frederic Dessauge

AbstractIn vivo study of tissue or organ biology in mammals is very complex and progress is slowed by poor accessibility of samples and ethical concerns. Fortunately, however, advances in stem cell identification and culture have made it possible to derive in vitro 3D “tissues” called organoids, these three-dimensional structures partly or fully mimicking the in vivo functioning of organs. The mammary gland produces milk, the source of nutrition for newborn mammals. Milk is synthesized and secreted by the differentiated polarized mammary epithelial cells of the gland. Reconstructing in vitro a mammary-like structure mimicking the functional tissue represents a major challenge in mammary gland biology, especially for farm animals for which specific agronomic questions arise. This would greatly facilitate the study of mammary gland development, milk secretion processes and pathological effects of viral or bacterial infections at the cellular level, all with the objective of improving milk production at the animal level. With this aim, various 3D cell culture models have been developed such as mammospheres and, more recently, efforts to develop organoids in vitro have been considerable. Researchers are now starting to draw inspiration from other fields, such as bioengineering, to generate organoids that would be more physiologically relevant. In this chapter, we will discuss 3D cell culture systems as organoids and their relevance for agronomic research.


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.


2019 ◽  
Vol 25 (34) ◽  
pp. 3599-3607 ◽  
Author(s):  
Adeeb Shehzad ◽  
Vijaya Ravinayagam ◽  
Hamad AlRumaih ◽  
Meneerah Aljafary ◽  
Dana Almohazey ◽  
...  

: The in-vitro experimental model for the development of cancer therapeutics has always been challenging. Recently, the scientific revolution has improved cell culturing techniques by applying three dimensional (3D) culture system, which provides a similar physiologically relevant in-vivo model for studying various diseases including cancer. In particular, cancer cells exhibiting in-vivo behavior in a model of 3D cell culture is a more accurate cell culture model to test the effectiveness of anticancer drugs or characterization of cancer cells in comparison with two dimensional (2D) monolayer. This study underpins various factors that cause resistance to anticancer drugs in forms of spheroids in 3D in-vitro cell culture and also outlines key challenges and possible solutions for the future development of these systems.


Polymers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 2506
Author(s):  
Advika Kamatar ◽  
Gokhan Gunay ◽  
Handan Acar

The lack of in vitro models that represent the native tumor microenvironment is a significant challenge for cancer research. Two-dimensional (2D) monolayer culture has long been the standard for in vitro cell-based studies. However, differences between 2D culture and the in vivo environment have led to poor translation of cancer research from in vitro to in vivo models, slowing the progress of the field. Recent advances in three-dimensional (3D) culture have improved the ability of in vitro culture to replicate in vivo conditions. Although 3D cultures still cannot achieve the complexity of the in vivo environment, they can still better replicate the cell–cell and cell–matrix interactions of solid tumors. Multicellular tumor spheroids (MCTS) are three-dimensional (3D) clusters of cells with tumor-like features such as oxygen gradients and drug resistance, and represent an important translational tool for cancer research. Accordingly, natural and synthetic polymers, including collagen, hyaluronic acid, Matrigel®, polyethylene glycol (PEG), alginate and chitosan, have been used to form and study MCTS for improved clinical translatability. This review evaluates the current state of biomaterial-based MCTS formation, including advantages and disadvantages of the different biomaterials and their recent applications to the field of cancer research, with a focus on the past five years.


2019 ◽  
Vol 24 (6) ◽  
pp. 615-627 ◽  
Author(s):  
Tijmen H. Booij ◽  
Leo S. Price ◽  
Erik H. J. Danen

The introduction of more relevant cell models in early preclinical drug discovery, combined with high-content imaging and automated analysis, is expected to increase the quality of compounds progressing to preclinical stages in the drug development pipeline. In this review we discuss the current switch to more relevant 3D cell culture models and associated challenges for high-throughput screening and high-content analysis. We propose that overcoming these challenges will enable front-loading the drug discovery pipeline with better biology, extracting the most from that biology, and, in general, improving translation between in vitro and in vivo models. This is expected to reduce the proportion of compounds that fail in vivo testing due to a lack of efficacy or to toxicity.


2020 ◽  
Vol 27 (16) ◽  
pp. 2734-2776 ◽  
Author(s):  
Gils Jose ◽  
K.T. Shalumon ◽  
Jyh-Ping Chen

It is well known that the extracellular matrix (ECM) plays a vital role in the growth, survival and differentiation of cells. Though two-dimensional (2D) materials are generally used as substrates for the standard in vitro experiments, their mechanical, structural, and compositional characteristics can alter cell functions drastically. Many scientists reported that cells behave more natively when cultured in three-dimensional (3D) environments than on 2D substrates, due to the more in vivo-like 3D cell culture environment that can better mimic the biochemical and mechanical properties of the ECM. In this regard, water-swollen network polymer-based materials called hydrogels are highly attractive for developing 3D ECM analogs due to their biocompatibility and hydrophilicity. Since hydrogels can be tuned and altered systematically, these materials can function actively in a defined culture medium to support long-term self-renewal of various cells. The physico-chemical and biological properties of the materials used for developing hydrogel should be tunable in accordance with culture needs. Various types of hydrogels derived either from natural or synthetic origins are currently being used for cell culture applications. In this review, we present an overview of various hydrogels based on natural polymers that can be used for cell culture, irrespective of types of applications. We also explain how each hydrogel is made, its source, pros and cons in biological applications with a special focus on regenerative engineering.


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Jingwen Xu ◽  
Guangyan Qi ◽  
Weiqun Wang ◽  
Xiuzhi Susan Sun

AbstractIn vitro cell culture models on monolayer surfaces (2D) have been widely adapted for identification of chemopreventive food compounds and food safety evaluation. However, the low correlation between 2D models and in vivo animal models has always been a concern; this gap is mainly caused by the lack of a three-dimensional (3D) extracellular microenvironment. In 2D models, cell behaviors and functionalities are altered, resulting in varied responses to external conditions (i.e., antioxidants) and hence leading to low predictability. Peptide hydrogel 3D scaffolding technologies, such as PGmatrix for cell culture, have been recently reported to grow organoid-like spheroids physiologically mimicking the 3D microenvironment that can be used as an in vitro 3D model for investigating cell activities, which is anticipated to improve the prediction rate. Thus, this review focuses on advances in 3D peptide hydrogels aiming to introduce 3D cell culture tools as in vitro 3D models for cancer-related research regarding food safety and nutraceuticals.


2010 ◽  
Vol 38 (4) ◽  
pp. 1072-1075 ◽  
Author(s):  
Daniel J. Maltman ◽  
Stefan A. Przyborski

Drug discovery programmes require accurate in vitro systems for drug screening and testing. Traditional cell culture makes use of 2D (two-dimensional) surfaces for ex vivo cell growth. In such environments, cells are forced to adopt unnatural characteristics, including aberrant flattened morphologies. Therefore there is a strong demand for new cell culture platforms which allow cells to grow and respond to their environment in a more realistic manner. The development of 3D (three-dimensional) alternative substrates for in vitro cell growth has received much attention, and it is widely acknowledged that 3D cell growth is likely to more accurately reflect the in vivo tissue environments from which cultured cells are derived. 3D cell growth techniques promise numerous advantages over 2D culture, including enhanced proliferation and differentiation of stem cells. The present review focuses on the development of scaffold technologies for 3D cell culture.


RSC Advances ◽  
2020 ◽  
Vol 10 (71) ◽  
pp. 43682-43703
Author(s):  
Fahima Akther ◽  
Peter Little ◽  
Zhiyong Li ◽  
Nam-Trung Nguyen ◽  
Hang T. Ta

Hydrogel-based artificial scaffolds and its incorporation with microfluidic devices play a vital role in shifting in vitro models from two-dimensional (2D) cell culture to in vivo like three-dimensional (3D) cell culture


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nathan Jeger-Madiot ◽  
Lousineh Arakelian ◽  
Niclas Setterblad ◽  
Patrick Bruneval ◽  
Mauricio Hoyos ◽  
...  

AbstractIn recent years, 3D cell culture models such as spheroid or organoid technologies have known important developments. Many studies have shown that 3D cultures exhibit better biomimetic properties compared to 2D cultures. These properties are important for in-vitro modeling systems, as well as for in-vivo cell therapies and tissue engineering approaches. A reliable use of 3D cellular models still requires standardized protocols with well-controlled and reproducible parameters. To address this challenge, a robust and scaffold-free approach is proposed, which relies on multi-trap acoustic levitation. This technology is successfully applied to Mesenchymal Stem Cells (MSCs) maintained in acoustic levitation over a 24-h period. During the culture, MSCs spontaneously self-organized from cell sheets to cell spheroids with a characteristic time of about 10 h. Each acoustofluidic chip could contain up to 30 spheroids in acoustic levitation and four chips could be ran in parallel, leading to the production of 120 spheroids per experiment. Various biological characterizations showed that the cells inside the spheroids were viable, maintained the expression of their cell surface markers and had a higher differentiation capacity compared to standard 2D culture conditions. These results open the path to long-time cell culture in acoustic levitation of cell sheets or spheroids for any type of cells.


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