A Review of Three-Dimensional In Vitro Tissue Models for Drug Discovery and Transport Studies

2011 ◽  
Vol 100 (1) ◽  
pp. 59-74 ◽  
Author(s):  
Nelita T. Elliott ◽  
Fan Yuan
Keyword(s):  
Drug Discovery ◽  
Three Dimensional ◽  
Transport Studies ◽  
Tissue Models

scholarly journals Human iPSC-Based Modeling of Central Nerve System Disorders for Drug Discovery

2021 ◽  
Vol 22 (3) ◽  
pp. 1203
Author(s):  
Lu Qian ◽  
Julia TCW
Keyword(s):  
Drug Discovery ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Structural Complexity ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Central Nerve System ◽  
Human Ipscs ◽  
Nerve System

A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients’ CNS and serve as a platform for therapeutic development and personalized precision medicine.

Easy and affordable method for rapid prototyping of tissue models in vitro using three-dimensional bioprinting

2018 ◽  
Vol 38 (1) ◽  
pp. 158-169 ◽  
Author(s):  
Ashutosh Bandyopadhyay ◽  
Vimal Kumar Dewangan ◽  
Kiran Yellappa Vajanthri ◽  
Suruchi Poddar ◽  
Sanjeev Kumar Mahto
Keyword(s):  
Rapid Prototyping ◽  
Three Dimensional ◽  
Tissue Models

scholarly journals Three-Dimensional Cell Cultures as an In Vitro Tool for Prostate Cancer Modeling and Drug Discovery

2020 ◽  
Vol 21 (18) ◽  
pp. 6806 ◽  
Author(s):  
Fabrizio Fontana ◽  
Michela Raimondi ◽  
Monica Marzagalli ◽  
Michele Sommariva ◽  
Nicoletta Gagliano ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Culture ◽  
Drug Discovery ◽  
Cancer Cells ◽  
Cell Cultures ◽  
Antitumor Agents ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Cancer Modeling

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.

scholarly journals Imaging and Analysis of Cellular Locations in Three-Dimensional Tissue Models

2019 ◽  
Vol 25 (3) ◽  
pp. 753-761 ◽  
Author(s):  
Warren Colomb ◽  
Matthew Osmond ◽  
Charles Durfee ◽  
Melissa D. Krebs ◽  
Susanta K. Sarkar
Keyword(s):  
Three Dimensional ◽  
Human Mesenchymal Stem Cells ◽  
Basic Research ◽  
Light Sheet ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions ◽  
Tissue Models ◽  
Alginate Matrix

AbstractThe absence of quantitative in vitro cell–extracellular matrix models represents an important bottleneck for basic research and human health. Randomness of cellular distributions provides an opportunity for the development of a quantitative in vitro model. However, quantification of the randomness of random cell distributions is still lacking. In this paper, we have imaged cellular distributions in an alginate matrix using a multiview light sheet microscope and developed quantification metrics of randomness by modeling it as a Poisson process, a process that has constant probability of occurring in space or time. We imaged fluorescently labeled human mesenchymal stem cells embedded in an alginate matrix of thickness greater than 5 mm with $\sim\! {\rm 2}{\rm. 9} \pm {\rm 0}{\rm. 4}\,\mu {\rm m}$ axial resolution, the mean full width at half maximum of the axial intensity profiles of fluorescent particles. Simulated randomness agrees well with the experiments. Quantification of distributions and validation by simulations will enable quantitative study of cell–matrix interactions in tissue models.

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

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Loh Teng Hern Tan ◽  
Liang Ee Low ◽  
Siah Ying Tang ◽  
Wei Hsum Yap ◽  
Lay Hong Chuah ◽  
...  
Keyword(s):  
Cell Culture ◽  
Drug Discovery ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Automated Image Analysis ◽  
Tumor Spheroids ◽  
Culture Methods ◽  
In Vivo Models

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

scholarly journals Application of hepatocyte-like cells to enhance hepatic safety risk assessment in drug discovery

2018 ◽  
Vol 373 (1750) ◽  
pp. 20170228 ◽  
Author(s):  
Dominic P. Williams
Keyword(s):  
Risk Assessment ◽  
Drug Discovery ◽  
High Throughput Screening ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
Genetic Characteristics ◽  
Short Period ◽  
Donor Variation ◽  
Discovery Pipeline

Hepatic stress and injury from drugs continues to be a major concern within the pharmaceutical industry, leading to preclinical and clinical attrition precautionary warnings and post-market withdrawal of drugs. There is a requirement for more predictive and mechanistically accurate models to aid risk assessment. Primary human hepatocytes, subject to isolation stress, cryopreservation, donor-to-donor variation and a relatively short period of functional capability in two-dimensional cultures, are not suitable for high-throughput screening procedures. There are two areas within the drug discovery pipeline that the generation of a stable, metabolically functional hepatocyte-like cell with unlimited supply would have major impact. First, in routine, cell health risk-assessment assays where hepatic cell lines are typically deployed. Second, at later stages of the drug discovery pipeline approaching candidate nomination where bespoke/investigational studies refining and understanding the risk to patients use patient-derived induced pluripotent stem cell (iPSC) hepatocytes retaining characteristics from the patient, e.g. HLA susceptibility alleles, iPSC hepatocytes with defined disease phenotypes or genetic characteristics that have the potential to make the hepatocyte more sensitive to a particular stress mechanism. Functionality of patient-centric hepatocyte-like cells is likely to be enhanced when coupled with emerging culture systems, such as three-dimensional spheroids or microphysiological systems. Ultimately, the aspiration to confidently use human-relevant in vitro models to predict human-specific hepatic toxicity depends on the integration of promising emerging technologies. This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.

scholarly journals An Innovative Cell Microincubator for Drug Discovery Based on 3D Silicon Structures

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Francesca Aredia ◽  
Francesca Carpignano ◽  
Salvatore Surdo ◽  
Giuseppe Barillaro ◽  
Giuliano Mazzini ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Tumor Cells ◽  
Three Dimensional ◽  
Label Free ◽  
Core Element ◽  
Great Ability ◽  
Label Free Detection ◽  
Ht1080 Cells ◽  
Power Radiation

We recently employed three-dimensional (3D) silicon microstructures (SMSs) consisting in arrays of 3 μm-thick silicon walls separated by 50 μm-deep, 5 μm-wide gaps, as microincubators for monitoring the biomechanical properties of tumor cells. They were here applied to investigate the in vitro behavior of HT1080 human fibrosarcoma cells driven to apoptosis by the chemotherapeutic drug Bleomycin. Our results, obtained by fluorescence microscopy, demonstrated that HT1080 cells exhibited a great ability to colonize the narrow gaps. Remarkably, HT1080 cells grown on 3D-SMS, when treated with the DNA damaging agent Bleomycin under conditions leading to apoptosis, tended to shrink, reducing their volume and mimicking the normal behavior of apoptotic cells, and were prone to leave the gaps. Finally, we performed label-free detection of cells adherent to the vertical silicon wall, inside the gap of 3D-SMS, by exploiting optical low coherence reflectometry using infrared, low power radiation. This kind of approach may become a new tool for increasing automation in the drug discovery area. Our results open new perspectives in view of future applications of the 3D-SMS as the core element of a lab-on-a-chip suitable for screening the effect of new molecules potentially able to kill tumor cells.

scholarly journals Soft Hydrogels Featuring In-Depth Surface Density Gradients for the Simple Establishment of 3D Tissue Models for Screening Applications

2017 ◽  
Vol 22 (5) ◽  
pp. 635-644
Author(s):  
Ning Zhang ◽  
Vincent Milleret ◽  
Greta Thompson-Steckel ◽  
Ning-Ping Huang ◽  
János Vörös ◽  
...  
Keyword(s):  
Three Dimensional ◽  
3D Cell Culture ◽  
Stem Cell Differentiation ◽  
Cancer Models ◽  
First Choice ◽  
Culture Models ◽  
Encapsulation Method ◽  
Tissue Models ◽  
Cell Culture Models

Three-dimensional (3D) cell culture models are gaining increasing interest for use in drug development pipelines due to their closer resemblance to human tissues. Hydrogels are the first-choice class of materials to recreate in vitro the 3D extra-cellular matrix (ECM) environment, important in studying cell-ECM interactions and 3D cellular organization and leading to physiologically relevant in vitro tissue models. Here we propose a novel hydrogel platform consisting of a 96-well plate containing pre-cast synthetic PEG-based hydrogels for the simple establishment of 3D (co-)culture systems without the need for the standard encapsulation method. The in-depth density gradient at the surface of the hydrogel promotes the infiltration of cells deposited on top of it. The ability to decouple hydrogel production and cell seeding is intended to simplify the use of hydrogel-based platforms and thus increase their accessibility. Using this platform, we established 3D cultures relevant for studying stem cell differentiation, angiogenesis, and neural and cancer models.

Three-Dimensional Tissue Models for Drug Discovery and Toxicology

2009 ◽  
Vol 3 (2) ◽  
pp. 103-117 ◽  
Author(s):  
Francesco Pampaloni ◽  
Ernst Stelzer ◽  
Andrea Masotti
Keyword(s):  
Drug Discovery ◽  
Three Dimensional ◽  
Tissue Models
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