scholarly journals Genotoxicity of Nanomaterials: Advanced In Vitro Models and High Throughput Methods for Human Hazard Assessment—A Review

Nanomaterials ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1911 ◽  
Author(s):  
Yvonne Kohl ◽  
Elise Rundén-Pran ◽  
Espen Mariussen ◽  
Michelle Hesler ◽  
Naouale El Yamani ◽  
...  
Keyword(s):  
High Throughput ◽  
State Of The Art ◽  
Genetic Material ◽  
3D Models ◽  
In Vitro Models ◽  
Current State ◽  
Genotoxic Compounds ◽  
Genome Level

Changes in the genetic material can lead to serious human health defects, as mutations in somatic cells may cause cancer and can contribute to other chronic diseases. Genotoxic events can appear at both the DNA, chromosomal or (during mitosis) whole genome level. The study of mechanisms leading to genotoxicity is crucially important, as well as the detection of potentially genotoxic compounds. We consider the current state of the art and describe here the main endpoints applied in standard human in vitro models as well as new advanced 3D models that are closer to the in vivo situation. We performed a literature review of in vitro studies published from 2000–2020 (August) dedicated to the genotoxicity of nanomaterials (NMs) in new models. Methods suitable for detection of genotoxicity of NMs will be presented with a focus on advances in miniaturization, organ-on-a-chip and high throughput methods.

scholarly journals O23: CHARACTERISING PATIENT-DERIVED COLORECTAL CANCER TISSUE-ORIGINATED ORGANOIDAL SPHEROIDS FOR HIGH-THROUGHPUT MICROFLUIDIC APPLICATIONS

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
MI Khot ◽  
M Levenstein ◽  
R Coppo ◽  
J Kondo ◽  
M Inoue ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fluid Flow ◽  
High Throughput ◽  
Microfluidic Devices ◽  
In Vitro Models ◽  
Fluorescent Imaging ◽  
Cancer Tissue ◽  
Cell Models

Abstract Introduction Three-dimensional (3D) cell models have gained reputation as better representations of in vivo cancers as compared to monolayered cultures. Recently, patient tumour tissue-derived organoids have advanced the scope of complex in vitro models, by allowing patient-specific tumour cultures to be generated for developing new medicines and patient-tailored treatments. Integrating 3D cell and organoid culturing into microfluidics, can streamline traditional protocols and allow complex and precise high-throughput experiments to be performed with ease. Method Patient-derived colorectal cancer tissue-originated organoidal spheroids (CTOS) cultures were acquired from Kyoto University, Japan. CTOS were cultured in Matrigel and stem-cell media. CTOS were treated with 5-fluorouracil and cytotoxicity evaluated via fluorescent imaging and ATP assay. CTOS were embedded, sectioned and subjected to H&E staining and immunofluorescence for ABCG2 and Ki67 proteins. HT29 colorectal cancer spheroids were produced on microfluidic devices using cell suspensions and subjected to 5-fluorouracil treatment via fluid flow. Cytotoxicity was evaluated through fluorescent imaging and LDH assay. Result 5-fluorouracil dose-dependent reduction in cell viability was observed in CTOS cultures (p<0.01). Colorectal CTOS cultures retained the histology, tissue architecture and protein expression of the colonic epithelial structure. Uniform 3D HT29 spheroids were generated in the microfluidic devices. 5-fluorouracil treatment of spheroids and cytotoxic analysis was achieved conveniently through fluid flow. Conclusion Patient-derived CTOS are better complex models of in vivo cancers than 3D cell models and can improve the clinical translation of novel treatments. Microfluidics can streamline high-throughput screening and reduce the practical difficulties of conventional organoid and 3D cell culturing. Take-home message Organoids are the most advanced in vitro models of clinical cancers. Microfluidics can streamline and improve traditional laboratory experiments.

scholarly journals The Role of Biomimetic Hypoxia on Cancer Cell Behaviour in 3D Models: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1334
Author(s):  
Ye Liu ◽  
Zahra Mohri ◽  
Wissal Alsheikh ◽  
Umber Cheema
Keyword(s):  
Systematic Review ◽  
Cellular Response ◽  
3D Culture ◽  
3D Models ◽  
In Vitro Models ◽  
Research Findings ◽  
Tissue Models

The development of biomimetic, human tissue models is recognized as being an important step for transitioning in vitro research findings to the native in vivo response. Oftentimes, 2D models lack the necessary complexity to truly recapitulate cellular responses. The introduction of physiological features into 3D models informs us of how each component feature alters specific cellular response. We conducted a systematic review of research papers where the focus was the introduction of key biomimetic features into in vitro models of cancer, including 3D culture and hypoxia. We analysed outcomes from these and compiled our findings into distinct groupings to ascertain which biomimetic parameters correlated with specific responses. We found a number of biomimetic features which primed cancer cells to respond in a manner which matched in vivo response.

scholarly journals In vitro and in vivo trematode models for chemotherapeutic studies

Parasitology ◽  
2009 ◽  
Vol 137 (3) ◽  
pp. 589-603 ◽  
Author(s):  
J. KEISER
Keyword(s):  
Liver Fluke ◽  
Fasciola Hepatica ◽  
State Of The Art ◽  
Parasitic Diseases ◽  
Current State ◽  
Food Borne ◽  
Essential Components ◽  
Discovery Pipeline

SUMMARYSchistosomiasis and food-borne trematodiases are chronic parasitic diseases affecting millions of people mostly in the developing world. Additional drugs should be developed as only few drugs are available for treatment and drug resistance might emerge. In vitro and in vivo whole parasite screens represent essential components of the trematodicidal drug discovery cascade. This review describes the current state-of-the-art of in vitro and in vivo screening systems of the blood fluke Schistosoma mansoni, the liver fluke Fasciola hepatica and the intestinal fluke Echinostoma caproni. Examples of in vitro and in vivo evaluation of compounds for activity are presented. To boost the discovery pipeline for these diseases there is a need to develop validated, robust high-throughput in vitro systems with simple readouts.

scholarly journals In vitro Models of the Small Intestine for Studying Intestinal Diseases

2022 ◽  
Vol 12 ◽  
Author(s):  
Sang-Myung Jung ◽  
Seonghun Kim
Keyword(s):  
Small Intestine ◽  
State Of The Art ◽  
Ex Vivo ◽  
3D Culture ◽  
In Vitro Models ◽  
Cellular Functions ◽  
Current State ◽  
Culture Models ◽  
Composition Structure

The small intestine is a digestive organ that has a complex and dynamic ecosystem, which is vulnerable to the risk of pathogen infections and disorders or imbalances. Many studies have focused attention on intestinal mechanisms, such as host–microbiome interactions and pathways, which are associated with its healthy and diseased conditions. This review highlights the intestine models currently used for simulating such normal and diseased states. We introduce the typical models used to simulate the intestine along with its cell composition, structure, cellular functions, and external environment and review the current state of the art for in vitro cell-based models of the small intestine system to replace animal models, including ex vivo, 2D culture, organoid, lab-on-a-chip, and 3D culture models. These models are described in terms of their structure, composition, and co-culture availability with microbiomes. Furthermore, we discuss the potential application for the aforementioned techniques to these in vitro models. The review concludes with a summary of intestine models from the viewpoint of current techniques as well as their main features, highlighting potential future developments and applications.

scholarly journals Evaluation of Novel Doxorubicin-Loaded Magnetic Wax Nanocomposite Vehicles as Cancer Combinatorial Therapy Agents

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 637
Author(s):  
Julia Jiménez-López ◽  
Lorena García-Hevia ◽  
Consolación Melguizo ◽  
Jose Prados ◽  
Manuel Bañobre-López ◽  
...  
Keyword(s):  
Preliminary Data ◽  
3D Models ◽  
In Vitro Models ◽  
Solid Tumours ◽  
Clinical Translation ◽  
Combinatorial Therapy ◽  
New Developments ◽  
In Vivo Tests

The development of nanotechnology-based solutions for cancer at a preclinical level advances at an astounding pace. So far, clinical translation of these new developments has not been able to keep the pace due to a range of different reasons. One of them is the mismatch between in vitro and in vivo results coming from the expected difference in complexity. To overcome this problem, extensive characterisation using advanced in vitro models can lead to stronger preliminary data to face in vivo tests. Here, a comprehensive in vitro validation of a combinatorial therapy nanoformulation against solid tumours is presented. The information extracted from the different in vitro models highlights the importance of advanced 3D models to fully understand the potential of this type of complex drugs.

scholarly journals Bioassays based on higher plants as excellent dosimeters for ecotoxicity monitoring: A review

2019 ◽  
Author(s):  
Chem Int ◽  
Munawar Iqbal
Keyword(s):  
Industrial Wastewater ◽  
Management Practices ◽  
Genetic Model ◽  
Higher Plants ◽  
Low Cost ◽  
Genetic Material ◽  
Industrial Effluents ◽  
In Vitro Models

All sorts of pollution on the planet can be traced back to development of industries and the most important among them is water pollution. Clean technologies, management practices and regular monitoring of effluents could be helpful to minimize the contamination of watersheds. Allium cepa (A. cepa) has been recognized as a promising genetic model to detect the toxicity of industrial wastewater, contaminated soil, river water, nuclear contamination and even for those systems which are considered non toxic. A. cepa is distinguished as a low cost test, easy to handle and sensitive to both in vivo and in vitro models. It offers the detection of damages in genetic material quantitatively and the results can be generalized for other biological and ecological systems. Moreover, the pollutants can be classified on the basis of this test present in industrial effluents and their mechanism of action on genetic material. This review focuses on the studies undertaken to evaluate the toxicity of industrial wastewater, contaminated river and soils.

scholarly journals Fracture Healing Research—Shift towards In Vitro Modeling?

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 748
Author(s):  
Moritz Pfeiffenberger ◽  
Alexandra Damerau ◽  
Annemarie Lang ◽  
Frank Buttgereit ◽  
Paula Hoff ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Ex Vivo ◽  
3D Models ◽  
In Vitro Models ◽  
Human Patient ◽  
In Vivo Models ◽  
Underlying Mechanisms ◽  
Biological Situation

Fractures are one of the most frequently occurring traumatic events worldwide. Approximately 10% of fractures lead to bone healing disorders, resulting in strain for affected patients and enormous costs for society. In order to shed light into underlying mechanisms of bone regeneration (habitual or disturbed), and to develop new therapeutic strategies, various in vivo, ex vivo and in vitro models can be applied. Undeniably, in vivo models include the systemic and biological situation. However, transferability towards the human patient along with ethical concerns regarding in vivo models have to be considered. Fostered by enormous technical improvements, such as bioreactors, on-a-chip-technologies and bone tissue engineering, sophisticated in vitro models are of rising interest. These models offer the possibility to use human cells from individual donors, complex cell systems and 3D models, therefore bridging the transferability gap, providing a platform for the introduction of personalized precision medicine and finally sparing animals. Facing diverse processes during fracture healing and thus various scientific opportunities, the reliability of results oftentimes depends on the choice of an appropriate model. Hence, we here focus on categorizing available models with respect to the requirements of the scientific approach.

scholarly journals Application of three-dimensional neuronal cell cultures in the studies of mechanisms of neurodegenerative diseases

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Anna Słońska ◽  
Joanna Cymerys
Keyword(s):  
Neurodegenerative Diseases ◽  
Cell Cultures ◽  
Three Dimensional ◽  
Neuronal Cell ◽  
3D Models ◽  
In Vitro Models ◽  
Gene And Protein Expression ◽  
Or Gene

In vitro models utilizing cells in planar two-dimensional (2D) cultures do not reflect the in vivo environment and are increasingly replaced by three-dimensional (3D) cultures. Fundamental differences between 2D and 3D cell cultures systems include cell attach, spread and grow, their morphology, proliferation, differentiation or gene and protein expression. For that reason 3D models have been proven to be invaluable tools of study for the various fields of science, such as drug discovery, cancer research, differentiation studies or neuroscience. In the present review, we discuss 3D neural in vitro models that might provide important insides about the mechanisms of pathogenesis of neurodegenerative diseases.

scholarly journals Translating genetic and preclinical findings into autism therapies

2017 ◽  
Vol 19 (4) ◽  
pp. 335-343
Keyword(s):  
Neurodevelopmental Disorder ◽  
Genetic Research ◽  
Autism Spectrum ◽  
In Vitro Models ◽  
Valuable Insight ◽  
Current State ◽  
Copy Number Changes ◽  
The Impact

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and repetitive/restrictive interests. ASD is associated with multiple comorbidities, including intellectual disability, anxiety, and epilepsy. Evidence that ASD is highly heritable has spurred major efforts to unravel its genetics, revealing possible contributions from hundreds of genes through rare and common variation and through copy-number changes. In this perspective, we provide an overview of the current state of ASD genetics and of how genetic research has spurred the development of in vivo and in vitro models using animals and patient cells to evaluate the impact of genetic mutations on cellular function leading to disease. Efforts to translate these findings into successful therapies have yet to bear fruit. We discuss how the valuable insight into the disorder provided by these new models can be used to better understand ASD and develop future clinical trials.

scholarly journals In Vitro and In Vivo Models to Assess the Immune-Related Effects of Nanomaterials

2021 ◽  
Vol 18 (22) ◽  
pp. 11769
Author(s):  
Diana Boraschi ◽  
Dongjie Li ◽  
Yang Li ◽  
Paola Italiani
Keyword(s):  
Real Life ◽  
Relevant Information ◽  
3D Models ◽  
In Vitro Models ◽  
Experimental Models ◽  
Human Beings ◽  
In Vivo Models ◽  
Advantages And Disadvantages

The immunological safety of drugs, nanomaterials and contaminants is a central point in the regulatory evaluation and safety monitoring of working and public places and of the environment. In fact, anomalies in immune responses may cause diseases and hamper the physical and functional integrity of living organisms, from plants to human beings. In the case of nanomaterials, many experimental models are used for assessing their immunosafety, some of which have been adopted by regulatory bodies. All of them, however, suffer from shortcomings and approximations, and may be inaccurate in representing real-life responses, thereby leading to incomplete, incorrect or even misleading predictions. Here, we review the advantages and disadvantages of current nanoimmunosafety models, comparing in vivo vs. in vitro models and examining the use of animal vs. human cells, primary vs. transformed cells, complex multicellular and 3D models, organoids and organs-on-chip, in view of implementing a reliable and personalized nanoimmunosafety testing. The general conclusion is that the choice of testing models is key for obtaining reliable predictive information, and therefore special attention should be devoted to selecting the most relevant and realistic suite of models in order to generate relevant information that can allow for safer-by-design nanotechnological developments.

Sign in / Sign up

Export Citation Format

Share Document