Application of Three-dimensional (3D) Tumor Cell Culture Systems and Mechanism of Drug Resistance

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.

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2754 ◽  
Author(s):  
Teruki Nii ◽  
Kimiko Makino ◽  
Yasuhiko Tabata

Anticancer drug screening is one of the most important research and development processes to develop new drugs for cancer treatment. However, there is a problem resulting in gaps between the in vitro drug screening and preclinical or clinical study. This is mainly because the condition of cancer cell culture is quite different from that in vivo. As a trial to mimic the in vivo cancer environment, there has been some research on a three-dimensional (3D) culture system by making use of biomaterials. The 3D culture technologies enable us to give cancer cells an in vitro environment close to the in vivo condition. Cancer cells modified to replicate the in vivo cancer environment will promote the biological research or drug discovery of cancers. This review introduces the in vitro research of 3D cell culture systems with biomaterials in addition to a brief summary of the cancer environment.


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.


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)...


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.


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


Nanomaterials ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 588 ◽  
Author(s):  
Jeong Hwa Kim ◽  
Ju Young Park ◽  
Songwan Jin ◽  
Sik Yoon ◽  
Jong-Young Kwak ◽  
...  

Recently, three-dimensional (3D) cell culture and tissue-on-a-chip application have attracted attention because of increasing demand from the industries and their potential to replace conventional two-dimensional culture and animal tests. As a result, numerous studies on 3D in-vitro cell culture and microfluidic chip have been conducted. In this study, a microfluidic chip embracing a nanofiber scaffold is presented. A electrospun nanofiber scaffold can provide 3D cell culture conditions to a microfluidic chip environment, and its perfusion method in the chip can allow real-time monitoring of cell status based on the conditioned culture medium. To justify the applicability of the developed chip to 3D cell culture and real-time monitoring, HepG2 cells were cultured in the chip for 14 days. Results demonstrated that the cells were successfully cultured with 3D culture-specific-morphology in the chip, and their albumin and alpha-fetoprotein production was monitored in real-time for 14 days.


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.


Author(s):  
Dong Pan ◽  
Yarong Du ◽  
Rong Li ◽  
Aihua Shen ◽  
Xiaodong Liu ◽  
...  

Radioresistance conferred by cancer stem cells (CSCs) is the principal cause of the failure of cancer radiotherapy. Eradication of CSCs is a prime therapeutic target and a requirement for effective radiotherapy. Three dimensional (3D) cell-cultured model could mimic the morphology of cells in vivo and induce CSC properties. Emerging evidence suggests that microRNAs (miRNAs) play crucial roles in the regulation of radiosensitivity in cancers. In this study, we aim to investigate the effects of miRNAs on the radiosensitivity of 3D cultured stem-like cells. Using miRNA microarray analysis in 2D and 3D cell culture models, we found that the expression of miR-29b-3p was downregulated in 3D cultured A549 and MCF7 cells compared with monolayer (2D) cells. Clinic data analysis from The Cancer Genome Atlas database exhibited that miR-29b-3p high expression showed significant advantages in lung adenocarcinoma and breast invasive carcinoma patients’ prognosis. The subsequent experiments proved that miR-29b-3p overexpression decreased the radioresistance of cells in 3D culture and tumors in vivo through interfering kinetics process of DNA damage repair and inhibiting oncogenes RBL1, PIK3R1, AKT2, and Bcl-2. In addition, miR-29b-3p knockdown enhanced cancer cells invasion and migration capability. MiR-29b-3p overexpression decreased the stemness of 3D cultured cells. In conclusion, our results demonstrate that miR-29b-3p could be a sensitizer of radiation killing in CSC-like cells via inhibiting oncogenes expression. MiR-29b-3p could be a novel therapeutic candidate target for radiotherapy.


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