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

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.

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Experimental Models in Rheumatoid Arthritis:

International Journal for Innovation Education and Research ◽

10.31686/ijier.vol8.iss1.2129 ◽

2020 ◽

Vol 8 (1) ◽

pp. 119-134

Author(s):

Verônica Assalin Zorgetto-Pinheiro ◽

Alexandre Meira de Vasconcelos ◽

Rafael Sanaiotte Pinheiro ◽

Danielle Bogo ◽

Iandara Schettert Silva

Keyword(s):

Rheumatoid Arthritis ◽

Drug Testing ◽

Pathological Condition ◽

In Vitro Models ◽

Experimental Models ◽

In Vivo Models ◽

Methodological Tool ◽

Class 1

Rheumatoid arthritis is an autoimmune and chronic pathological condition characterized by an inflammatory process of the joints It is a complex and multifactorial, involving genetic, epigenetic and environmental factors and the use of experimental models is required to better understand its pathology and for drug testing. The aim of this study was to perform a systematic literature review on experimental models in rheumatoid arthritis using IRAMUTEQ, a software that analysis, qualitatively and quantitatively, text fragments, as a methodological tool. After searching for articles published in the last five years on Scopus database and applying the exclusion criteria, we ended with 84 articles. The most commonly employed experimental models was the arthritis induction by inoculation of the Complete Freund's Adjuvant (CFA), followed by the use of combined methodologies and the collagen-induced arthritis (CIA). The analyses of abstracts by the IRAMUTEQ software provided a classification according to their textual elements in four classes, which were grouped into three main themes: in vivo models (class 1), clinical practice and traditional medicine (classes 2 and 3) and in vitro models (class 4) and it was also possible to build a similarity tree of the terms present in the abstracts and a word cloud with the most cited terms. Thus, the use of the IRAMUTEQ software as a methodological tool has been satisfactory, since it was possible to identify the main experimental models used, keywords, pathological processes and molecules involved in the pathogenesis of rheumatoid arthritis free of the researchers’ bias, in addition to being a tool for visual and intuitive results.

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Experimental Models as Refined Translational Tools for Breast Cancer Research

Scientia Pharmaceutica ◽

10.3390/scipharm88030032 ◽

2020 ◽

Vol 88 (3) ◽

pp. 32

Author(s):

Eduardo Costa ◽

Tânia Ferreira-Gonçalves ◽

Gonçalo Chasqueira ◽

António S. Cabrita ◽

Isabel V. Figueiredo ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Research ◽

Animal Models ◽

In Vitro Models ◽

Experimental Models ◽

Breast Cancer Research ◽

Breast Cancers ◽

In Vivo Models

Breast cancer is one of the most common cancers worldwide, which makes it a very impactful malignancy in the society. Breast cancers can be classified through different systems based on the main tumor features and gene, protein, and cell receptors expression, which will determine the most advisable therapeutic course and expected outcomes. Multiple therapeutic options have already been proposed and implemented for breast cancer treatment. Nonetheless, their use and efficacy still greatly depend on the tumor classification, and treatments are commonly associated with invasiveness, pain, discomfort, severe side effects, and poor specificity. This has demanded an investment in the research of the mechanisms behind the disease progression, evolution, and associated risk factors, and on novel diagnostic and therapeutic techniques. However, advances in the understanding and assessment of breast cancer are dependent on the ability to mimic the properties and microenvironment of tumors in vivo, which can be achieved through experimentation on animal models. This review covers an overview of the main animal models used in breast cancer research, namely in vitro models, in vivo models, in silico models, and other models. For each model, the main characteristics, advantages, and challenges associated to their use are highlighted.

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Fracture Healing Research—Shift towards In Vitro Modeling?

Biomedicines ◽

10.3390/biomedicines9070748 ◽

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.

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In Vitro and In Vivo Models for the Investigation of Potential Drugs Against Schizophrenia

Biomolecules ◽

10.3390/biom10010160 ◽

2020 ◽

Vol 10 (1) ◽

pp. 160

Author(s):

Oliwia Koszła ◽

Katarzyna M. Targowska-Duda ◽

Ewa Kędzierska ◽

Agnieszka A. Kaczor

Keyword(s):

Experimental Studies ◽

In Vitro Models ◽

Experimental Models ◽

Critical Discussion ◽

New Drugs ◽

Complex Nature ◽

Cognitive Symptoms ◽

In Vivo Models

Schizophrenia (SZ) is a complex psychiatric disorder characterized by positive, negative, and cognitive symptoms, and is not satisfactorily treated by current antipsychotics. Progress in understanding the basic pathomechanism of the disease has been hampered by the lack of appropriate models. In order to develop modern drugs against SZ, efficient methods to study them in in vitro and in vivo models of this disease are required. In this review a short presentation of current hypotheses and concepts of SZ is followed by a description of current progress in the field of SZ experimental models. A critical discussion of advantages and limitations of in vitro models and pharmacological, genetic, and neurodevelopmental in vivo models for positive, negative, and cognitive symptoms of the disease is provided. In particular, this review concerns the important issue of how cellular and animal systems can help to meet the challenges of modeling the disease, which fully manifests only in humans, as experimental studies of SZ in humans are limited. Next, it is emphasized that novel clinical candidates should be evaluated in animal models for treatment-resistant SZ. In conclusion, the plurality of available in vitro and in vivo models is a consequence of the complex nature of SZ, and there are extensive possibilities for their integration. Future development of more efficient antipsychotics reflecting the pleiotropy of symptoms in SZ requires the incorporation of various models into one uniting model of the multifactorial disorder and use of this model for the evaluation of new drugs.

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Polysaccharides with Antitumor Effect in Breast Cancer: A Systematic Review of Non-Clinical Studies

Nutrients ◽

10.3390/nu13062008 ◽

2021 ◽

Vol 13 (6) ◽

pp. 2008

Author(s):

Claudia Rita Corso ◽

Natalia Mulinari Turin de Oliveira ◽

Leonardo Moura Cordeiro ◽

Karien Sauruk da Silva ◽

Suzany Hellen da Silva Soczek ◽

...

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Cellular Proliferation ◽

In Vitro Models ◽

Mechanisms Of Action ◽

Experimental Models ◽

In Vivo Models ◽

Apoptosis Inhibition

Purpose: To review the effects of polysaccharides and their proposed mechanisms of action in breast cancer experimental models. Data sources, selection, and extraction: Articles were selected by using PubMed, ScienceDirect, Scopus, and Medline, assessed from 1 May 2019 to 1 July 2020. The systematic review was registered in the International Prospective Register of Systematic Reviews (Prospero) under the number CRD42020169103. Results: Most of the studies explore algae polysaccharides (43.2%), followed by mushrooms (13.5%), plants (13.5%), fruits (10.8%), fungus (2.7%), bacteria, (2.7%), and sea animals (2.7%). A total of 8.1% investigated only in vitro models, 62.1% evaluated only in vivo models, and 29.7% evaluated in vitro and in vivo models. The mechanism of action involves apoptosis, inhibition of cellular proliferation, angiogenesis, and antimetastatic effects through multiple pathways. Conclusions: Findings included here support further investigations on the anti-tumor effect of polysaccharides. Some polysaccharides, such as fucoidan and β-glucans, deserve detailed and structured studies aiming at translational research on breast tumors, since they are already used in the clinical practice of other proposals of human health.

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Looking for In Vitro Models for Retinal Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms221910334 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10334

Author(s):

Margherita Alfonsetti ◽

Vanessa Castelli ◽

Michele d’Angelo ◽

Elisabetta Benedetti ◽

Marcello Allegretti ◽

...

Keyword(s):

Visual Function ◽

Retinal Disease ◽

3D Models ◽

In Vitro Models ◽

Retinal Diseases ◽

In Vivo Models ◽

In Vivo Experiments ◽

Toxicological Studies

Retina is a layered structure of the eye, composed of different cellular components working together to produce a complex visual output. Because of its important role in visual function, retinal pathologies commonly represent the main causes of visual injury and blindness in the industrialized world. It is important to develop in vitro models of retinal diseases to use them in first screenings before translating in in vivo experiments and clinics. For this reason, it is important to develop bidimensional (2D) models that are more suitable for drug screening and toxicological studies and tridimensional (3D) models, which can replicate physiological conditions, for investigating pathological mechanisms leading to visual loss. This review provides an overview of the most common retinal diseases, relating to in vivo models, with a specific focus on alternative 2D and 3D in vitro models that can replicate the different cellular and matrix components of retinal layers, as well as injury insults that induce retinal disease and loss of the visual function.

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Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

Cancers ◽

10.3390/cancers13153651 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3651

Author(s):

Alexandru Blidisel ◽

Iasmina Marcovici ◽

Dorina Coricovac ◽

Florin Hut ◽

Cristina Adriana Dehelean ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Molecular Mechanisms ◽

Prediction Models ◽

3D Models ◽

Experimental Models ◽

Health Concern ◽

Liver Carcinoma ◽

Tumor Type

Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

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Experimental Models for Studying HPV-Positive and HPV-Negative Penile Cancer: New Tools for An Old Disease

Cancers ◽

10.3390/cancers13030460 ◽

2021 ◽

Vol 13 (3) ◽

pp. 460

Author(s):

Beatriz Medeiros-Fonseca ◽

Antonio Cubilla ◽

Haissa Brito ◽

Tânia Martins ◽

Rui Medeiros ◽

...

Keyword(s):

Mouse Models ◽

Cell Lines ◽

Penile Cancer ◽

Hpv Infection ◽

Experimental Models ◽

In Vivo Models ◽

Recent Developments ◽

Key Aspects

Penile cancer is an uncommon malignancy that occurs most frequently in developing countries. Two pathways for penile carcinogenesis are currently recognized: one driven by human papillomavirus (HPV) infection and another HPV-independent route, associated with chronic inflammation. Progress on the clinical management of this disease has been slow, partly due to the lack of preclinical models for translational research. However, exciting recent developments are changing this landscape, with new in vitro and in vivo models becoming available. These include mouse models for HPV+ and HPV− penile cancer and multiple cell lines representing HPV− lesions. The present review addresses these new advances, summarizing available models, comparing their characteristics and potential uses and discussing areas that require further improvement. Recent breakthroughs achieved using these models are also discussed, particularly those developments pertaining to HPV-driven cancer. Two key aspects that still require improvement are the establishment of cell lines that can represent HPV+ penile carcinomas and the development of mouse models to study metastatic disease. Overall, the growing array of in vitro and in vivo models for penile cancer provides new and useful tools for researchers in the field and is expected to accelerate pre-clinical research on this disease.

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

Cancers ◽

10.3390/cancers13061334 ◽

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.

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Bioreactors as physiologicallike in vitro models

Biomedical Science and Engineering ◽

10.4081/bse.2019.94 ◽

2020 ◽

Author(s):

Sara Mantero ◽

Federica Boschetti

Keyword(s):

Culture Conditions ◽

In Vitro Models ◽

In Vivo Models ◽

In Vitro Development ◽

Culture Cells ◽

Vitro Development ◽

Tissue Models ◽

Mechanical Stretching

Bioreactors are powerful tools for in vitro development of engineered substitutes through controlled biological, physical, and mechanical culture conditions: bioreactor technology allows a closer in vitro replication of native tissues. One of bioreactors applications is the design of in vitro 3D tissue models as a bridge between 2D and in vivo models, allowing the application of 3R (replacement, reduction, refinement) principle. To this aim, bioreactors can be used to culture cells seeded on engineered scaffolds under in vivo-like conditions. Another key use of bioreactors is for perfusion decellularization of tissues and organs to be used as scaffolds. This contribution describes a dynamic stretching. bioreactor, imposing a mechanical stretching to the cultured constructs, allowing the development of skeletal muscle engineered constructs, and a decellularization bioreactor, designed for decellularization of blood vessels.

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