scholarly journals Development of In Vitro Corneal Models: Opportunity for Pharmacological Testing

2020 ◽  
Vol 3 (4) ◽  
pp. 74
Author(s):  
Valentina Citi ◽  
Eugenia Piragine ◽  
Simone Brogi ◽  
Sara Ottino ◽  
Vincenzo Calderone
Keyword(s):  
Three Dimensional ◽  
Toxicity Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Rapid Expansion ◽  
Anatomy And Physiology ◽  
Complex Anatomy ◽  
Computational Procedures ◽  
Scientific Challenge

The human eye is a specialized organ with a complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years, many in vitro models have been developed in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review, the ocular cell types and functionality are described, providing an overview about the scientific challenge for the development of three-dimensional (3D) in vitro models.

scholarly journals Development of In Vitro Corneal Models: Opportunity for Pharmacological Testing and Legislative Aspects

2020 ◽  
Author(s):  
Valentina Citi ◽  
Eugenia Piragine ◽  
Simone Brogi ◽  
Sara Ottino ◽  
Marco Sansò ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Toxicity Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Rapid Expansion ◽  
Anatomy And Physiology ◽  
Complex Anatomy ◽  
Computational Procedures ◽  
Scientific Challenge

Human eye is a specialized organ with complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years many in vitro models have been developed, in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing which is necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria and are clearly labelled. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review the ocular cell types and functionality are described providing an overview about the scientific challenge for the development of three-dimensional in vitro models.

scholarly journals Development of In Vitro Corneal Models: Opportunity for Pharmacological Testing

2020 ◽  
Author(s):  
Valentina Citi ◽  
Eugenia Piragine ◽  
Simone Brogi ◽  
Sara Ottino ◽  
Vincenzo Calderone
Keyword(s):  
Three Dimensional ◽  
Toxicity Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Rapid Expansion ◽  
Anatomy And Physiology ◽  
Complex Anatomy ◽  
Computational Procedures ◽  
Scientific Challenge

Human eye is a specialized organ with complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years many in vitro models have been developed, in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review the ocular cell types and functionality are described providing an overview about the scientific challenge for the development of three-dimensional in vitro models.

scholarly journals Modelling the Human Placental Interface In Vitro—A Review

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 884
Author(s):  
Marta Cherubini ◽  
Scott Erickson ◽  
Kristina Haase
Keyword(s):  
Drug Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Placental Development ◽  
Scientific Challenge ◽  
Induced Pluripotent ◽  
And Function ◽  
And Control

Acting as the primary link between mother and fetus, the placenta is involved in regulating nutrient, oxygen, and waste exchange; thus, healthy placental development is crucial for a successful pregnancy. In line with the increasing demands of the fetus, the placenta evolves throughout pregnancy, making it a particularly difficult organ to study. Research into placental development and dysfunction poses a unique scientific challenge due to ethical constraints and the differences in morphology and function that exist between species. Recently, there have been increased efforts towards generating in vitro models of the human placenta. Advancements in the differentiation of human induced pluripotent stem cells (hiPSCs), microfluidics, and bioprinting have each contributed to the development of new models, which can be designed to closely match physiological in vivo conditions. By including relevant placental cell types and control over the microenvironment, these new in vitro models promise to reveal clues to the pathogenesis of placental dysfunction and facilitate drug testing across the maternal–fetal interface. In this minireview, we aim to highlight current in vitro placental models and their applications in the study of disease and discuss future avenues for these in vitro models.

scholarly journals Three-dimensional testicular organoids as novel in vitro models of testicular biology and toxicology

2019 ◽  
Vol 5 (3) ◽  
Author(s):  
Sadman Sakib ◽  
Anna Voigt ◽  
Taylor Goldsmith ◽  
Ina Dobrinski
Keyword(s):  
Reproductive Biology ◽  
Monolayer Culture ◽  
Three Dimensional ◽  
Cell Types ◽  
In Vitro Models ◽  
Toxicity Screening ◽  
Current State ◽  
Potential Applications ◽  
Multiple Cell

Abstract Organoids are three dimensional structures consisting of multiple cell types that recapitulate the cellular architecture and functionality of native organs. Over the last decade, the advent of organoid research has opened up many avenues for basic and translational studies. Following suit of other disciplines, research groups working in the field of male reproductive biology have started establishing and characterizing testicular organoids. The three-dimensional architectural and functional similarities of organoids to their tissue of origin facilitate study of complex cell interactions, tissue development and establishment of representative, scalable models for drug and toxicity screening. In this review, we discuss the current state of testicular organoid research, their advantages over conventional monolayer culture and their potential applications in the field of reproductive biology and toxicology.

scholarly journals In vitro models of the human heart

Development ◽  
2021 ◽  
Vol 148 (16) ◽  
Author(s):  
Pablo Hofbauer ◽  
Stefan M. Jahnel ◽  
Sasha Mendjan
Keyword(s):  
Heart Development ◽  
Human Heart ◽  
Three Dimensional ◽  
Cell Types ◽  
In Vitro Models ◽  
Major Bottleneck ◽  
Key Aspects ◽  
New Generation ◽  
Self Organizing

ABSTRACT Cardiac congenital disabilities are the most common organ malformations, but we still do not understand how they arise in the human embryo. Moreover, although cardiovascular disease is the most common cause of death globally, the development of new therapies is lagging compared with other fields. One major bottleneck hindering progress is the lack of self-organizing human cardiac models that recapitulate key aspects of human heart development, physiology and disease. Current in vitro cardiac three-dimensional systems are either engineered constructs or spherical aggregates of cardiomyocytes and other cell types. Although tissue engineering enables the modeling of some electro-mechanical properties, it falls short of mimicking heart development, morphogenetic defects and many clinically relevant aspects of cardiomyopathies. Here, we review different approaches and recent efforts to overcome these challenges in the field using a new generation of self-organizing embryonic and cardiac organoids.

Comparative Cell Toxicology: The Basis for In Vitro Toxicity Testing

1994 ◽  
Vol 22 (3) ◽  
pp. 168-174
Author(s):  
Hasso Seibert ◽  
Michael Gulden ◽  
Jens-Uwe Voss
Keyword(s):  
Toxicity Testing ◽  
Cell Types ◽  
Scientific Basis ◽  
In Vitro Models ◽  
In Vitro Toxicity ◽  
Full Potential ◽  
Type B ◽  
Cell Type ◽  
In Vitro Systems

If “cell toxicology” is defined as the discipline aimed at studying the general principles of chemical interference with cellular structures and/or functions, then “comparative cell toxicology” may be defined as the study of the variety of responses to xenobiotics using: (a) different endpoints within one cell type; (b) cell types from different tissues from one species; and (c) homologous cell types from different species. If the full potential of in vitro models for toxicity testing is to be realised and the scientific basis for hazard assessment improved, then comparative cell toxicological approaches have to be developed further. In the present paper, an approach using different in vitro systems is described. The approach is aimed at the assessment of the basic toxicological characteristics of chemicals.

scholarly journals Three-Dimensional Biofabrication Models of Endometriosis and the Endometriotic Microenvironment

2020 ◽  
Author(s):  
Jillian R. H. Wendel ◽  
Xiyin Wang ◽  
Lester J. Smith ◽  
Shannon M. Hawkins
Keyword(s):  
Cell Line ◽  
Three Dimensional ◽  
Uterine Cavity ◽  
Building Blocks ◽  
Cell Types ◽  
In Vitro Models ◽  
Inflammatory Factors ◽  
Biologically Relevant ◽  
Increased Risk

Endometriosis occurs when endometrial-like tissue grows outside the uterine cavity, leading to pelvic pain, infertility, and increased risk of ovarian cancer. The present study describes the optimization and characterization of cellular spheroids as building blocks for Kenzan scaffold-free method biofabrication and proof-of-concept models of endometriosis and the endometriotic microenvironment. The spheroid building blocks must be a specific diameter (~500 m), compact, round, and smooth to withstand Kenzan biofabrication. Under optimized spheroid conditions for biofabrication, the endometriotic epithelial-like cell line, 12Z, expressed high levels of estrogen-related genes and secreted high amounts of endometriotic inflammatory factors that were independent of TNF stimulation. Heterotypic spheroids, composed of 12Z and T-HESC, an immortalized endometrial stromal cell line, self-assembled into a biologically relevant pattern, consisting of epithelial cells on the outside of the spheroids and stromal cells in the core. 12Z spheroids were biofabricated into large three-dimensional constructs alone, with HEYA8 spheroids, or as heterotypic spheroids with T-HESC. These three-dimensional biofabricated constructs containing multiple monotypic or heterotypic spheroids represent the first scaffold-free biofabricated in vitro models of endometriosis and the endometriotic microenvironment. These efficient and innovative models will allow us to study the complex interactions of multiple cell types within a biologically relevant microenvironment.

A Human Corneal Equivalent Constructed from SV40-immortalised Corneal Cell Lines

2005 ◽  
Vol 33 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Michaela Zorn-Kruppa ◽  
Svitlana Tykhonova ◽  
Gazanfer Belge ◽  
Jürgen Bednarz ◽  
Horst A. Diehl ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cross Sections ◽  
Three Dimensional ◽  
Morphological Characteristics ◽  
Drug Efficacy ◽  
Collagen Matrix ◽  
Cell Types ◽  
In Vitro Models ◽  
Equivalent Model

Within the last decade, extensive research in the field of tissue and organ engineering has focused on the development of in vitro models of the cornea. The use of organotypic, three-dimensional corneal equivalents has several advantages over simple monolayer cultures. The aim of this study was to develop a corneal equivalent model composed of the same cell types as in the natural human tissue, but by using immortalised cell lines to ensure reproducibility and to minimise product variation. We report our success in the establishment of an SV40-immortalised human corneal keratocyte cell line (designated HCK). A collagen matrix, built up with these cells, displayed the morphological characteristics of the human stromal tissue and served as a biomatrix for the immortalised human corneal epithelial and endothelial cells. Histological cross-sections of the whole-cornea equivalents resemble human corneas in tissue structure. This organotypic in vitro model may serve as a research tool for the ophthalmic science community, as well as a model system for testing for eye irritancy and drug efficacy.

ten years of modelling to achieve haemodynamic optimisation of the total cavopulmonary connection

2004 ◽  
Vol 14 (S3) ◽  
pp. 48-52 ◽  
Author(s):  
gabriele dubini ◽  
francesco migliavacca ◽  
giancarlo pennati ◽  
marc r. de leval ◽  
edward l. bove
Keyword(s):  
Fluid Dynamics ◽  
Computational Fluid Dynamics ◽  
Cardiovascular System ◽  
Three Dimensional ◽  
In Vitro Models ◽  
Surgical Reconstruction ◽  
Complex Anatomy ◽  
Recent Developments ◽  
Three Dimensional Models

the techniques of computational fluid dynamics are among the most powerful tools available to engineers dealing with the motion of fluids and the exchange of mass, momentum, and energy. they have recently been shown to have an increasing number of applications to the human cardiovascular system, including the fluid dynamics of surgical reconstruction of congenitally malformed parts of the cardiovascular system. in vitro models are the alternative laboratory tools with which to study fluid dynamics. the advantages of computational fluid dynamics over the in vitro models are the easy quantification of haemodynamic variables, such as rates of flow, pressure, and distribution of shear stress, and changes in geometric and fluid dynamics parameters. furthermore, using computational fluid dynamics allows the development of three-dimensional models to reproduce both the complex anatomy of the investigated region and the details of the surgical reconstruction, especially with the recent developments in magnetic resonance imaging. on the basis of the results, it is possible quantitatively to evaluate the surgical correction. this technology, which benefits greatly from the continuous improvement in hardware and software, enables cardiovascular experts and bioengineers to look at the fluid dynamics of various cardiovascular regions with increasing sophistication.

scholarly journals Three-Dimensional Biofabrication Models of Endometriosis and the Endometriotic Microenvironment

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 525
Author(s):  
Jillian R. H. Wendel ◽  
Xiyin Wang ◽  
Lester J. Smith ◽  
Shannon M. Hawkins
Keyword(s):  
Cell Line ◽  
Three Dimensional ◽  
Uterine Cavity ◽  
Building Blocks ◽  
Cell Types ◽  
In Vitro Models ◽  
Inflammatory Factors ◽  
Biologically Relevant ◽  
Increased Risk

Endometriosis occurs when endometrial-like tissue grows outside the uterine cavity, leading to pelvic pain, infertility, and increased risk of ovarian cancer. The present study describes the optimization and characterization of cellular spheroids as building blocks for Kenzan scaffold-free method biofabrication and proof-of-concept models of endometriosis and the endometriotic microenvironment. The spheroid building blocks must be of a specific diameter (~500 μm), compact, round, and smooth to withstand Kenzan biofabrication. Under optimized spheroid conditions for biofabrication, the endometriotic epithelial-like cell line, 12Z, expressed high levels of estrogen-related genes and secreted high amounts of endometriotic inflammatory factors that were independent of TNFα stimulation. Heterotypic spheroids, composed of 12Z and T-HESC, an immortalized endometrial stromal cell line, self-assembled into a biologically relevant pattern, consisting of epithelial cells on the outside of the spheroids and stromal cells in the core. 12Z spheroids were biofabricated into large three-dimensional constructs alone, with HEYA8 spheroids, or as heterotypic spheroids with T-HESC. These three-dimensional biofabricated constructs containing multiple monotypic or heterotypic spheroids represent the first scaffold-free biofabricated in vitro models of endometriosis and the endometriotic microenvironment. These efficient and innovative models will allow us to study the complex interactions of multiple cell types within a biologically relevant microenvironment.

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