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 Current Advances in 3D Tissue and Organ Reconstruction

2021 ◽  
Vol 22 (2) ◽  
pp. 830
Author(s):  
Georgia Pennarossa ◽  
Sharon Arcuri ◽  
Teresina De Iorio ◽  
Fulvio Gandolfi ◽  
Tiziana A. L. Brevini
Keyword(s):  
Cell Biology ◽  
Drug Testing ◽  
Three Dimensional ◽  
3D Culture ◽  
In Vitro Models ◽  
The Body ◽  
Cellular Functions ◽  
Culture Systems

Bi-dimensional culture systems have represented the most used method to study cell biology outside the body for over a century. Although they convey useful information, such systems may lose tissue-specific architecture, biomechanical effectors, and biochemical cues deriving from the native extracellular matrix, with significant alterations in several cellular functions and processes. Notably, the introduction of three-dimensional (3D) platforms that are able to re-create in vitro the structures of the native tissue, have overcome some of these issues, since they better mimic the in vivo milieu and reduce the gap between the cell culture ambient and the tissue environment. 3D culture systems are currently used in a broad range of studies, from cancer and stem cell biology, to drug testing and discovery. Here, we describe the mechanisms used by cells to perceive and respond to biomechanical cues and the main signaling pathways involved. We provide an overall perspective of the most recent 3D technologies. Given the breadth of the subject, we concentrate on the use of hydrogels, bioreactors, 3D printing and bioprinting, nanofiber-based scaffolds, and preparation of a decellularized bio-matrix. In addition, we report the possibility to combine the use of 3D cultures with functionalized nanoparticles to obtain highly predictive in vitro models for use in the nanomedicine field.

scholarly journals Traditional and Advanced Cell Cultures in Hematopoietic Stem Cell Studies

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1628 ◽  
Author(s):  
Antonio Carlos Ribeiro-Filho ◽  
Débora Levy ◽  
Jorge Luis Maria Ruiz ◽  
Marluce da Cunha Mantovani ◽  
Sérgio Paulo Bydlowski
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Ex Vivo ◽  
3D Culture ◽  
Bone Marrow Microenvironment ◽  
Main Function ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Culture Models

Hematopoiesis is the main function of bone marrow. Human hematopoietic stem and progenitor cells reside in the bone marrow microenvironment, making it a hotspot for the development of hematopoietic diseases. Numerous alterations that correspond to disease progression have been identified in the bone marrow stem cell niche. Complex interactions between the bone marrow microenvironment and hematopoietic stem cells determine the balance between the proliferation, differentiation and homeostasis of the stem cell compartment. Changes in this tightly regulated network can provoke malignant transformation. However, our understanding of human hematopoiesis and the associated niche biology remains limited due to accessibility to human material and the limits of in vitro culture models. Traditional culture systems for human hematopoietic studies lack microenvironment niches, spatial marrow gradients, and dense cellularity, rendering them incapable of effectively translating marrow physiology ex vivo. This review will discuss the importance of 2D and 3D culture as a physiologically relevant system for understanding normal and abnormal hematopoiesis.

scholarly journals Sustained Ca2+ mobilizations: a quantitative approach to predict their importance in cell-cell communication and wound healing

2019 ◽  
Author(s):  
Yoonjoo Lee ◽  
Min Tae Kim ◽  
Garrett Rhodes ◽  
Kelsey Sack ◽  
Sung Jun Son ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ex Vivo ◽  
Cell Communication ◽  
In Vitro Models ◽  
Wound Edge ◽  
Communication Events ◽  
Epithelial Wound Healing ◽  
Culture Models ◽  
Cell Cell

AbstractEpithelial wound healing requires the coordination of cells to migrate as a unit over the basement membrane after injury. To understand the process of this coordinated movement, it is critical to study the dynamics of cell-cell communication. We developed a method to characterize the injury-induced sustained Ca2+ mobilizations that travel between cells for periods of time up to several hours. These events of communication are concentrated along the wound edge and are reduced in cells further away from the wound. Our goal was to delineate the role and contribution of these sustained mobilizations and using MATLAB analyses, we determined the probability of cell-cell communication events in in vitro models and ex vivo organ culture models. We demonstrated that the injury response was complex and represented the activation of a number of receptors. In addition, we found that pannexin channels mediated the cell-cell communication and motility. Furthermore, the sustained Ca2+ mobilizations are associated with changes in cell morphology and motility during wound healing. The results demonstrate that both purinoreceptors and pannexins regulate the sustained Ca2+ mobilization necessary for cell-cell communication in wound healing.

scholarly journals 3D in vitro models of skeletal muscle: myopshere, myobundle and bioprinted muscle construct

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Frederic Dessauge ◽  
Cindy Schleder ◽  
Marie-Hélène Perruchot ◽  
Karl Rouger
Keyword(s):  
Skeletal Muscle ◽  
Spatial Organization ◽  
3D Culture ◽  
Cell Types ◽  
In Vitro Models ◽  
Skeletal Muscle Function ◽  
Muscle Tissues ◽  
Culture Models ◽  
Living Tissues

AbstractTypical two-dimensional (2D) culture models of skeletal muscle-derived cells cannot fully recapitulate the organization and function of living muscle tissues, restricting their usefulness in in-depth physiological studies. The development of functional 3D culture models offers a major opportunity to mimic the living tissues and to model muscle diseases. In this respect, this new type of in vitro model significantly increases our understanding of the involvement of the different cell types present in the formation of skeletal muscle and their interactions, as well as the modalities of response of a pathological muscle to new therapies. This second point could lead to the identification of effective treatments. Here, we report the significant progresses that have been made the last years to engineer muscle tissue-like structures, providing useful tools to investigate the behavior of resident cells. Specifically, we interest in the development of myopshere- and myobundle-based systems as well as the bioprinting constructs. The electrical/mechanical stimulation protocols and the co-culture systems developed to improve tissue maturation process and functionalities are presented. The formation of these biomimetic engineered muscle tissues represents a new platform to study skeletal muscle function and spatial organization in large number of physiological and pathological contexts.

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.

3D Culture Modelling: An Emerging Approach for Translational Cancer Research in Sarcomas

2020 ◽  
Vol 27 (29) ◽  
pp. 4778-4788 ◽  
Author(s):  
Victoria Heredia-Soto ◽  
Andrés Redondo ◽  
José Juan Pozo Kreilinger ◽  
Virginia Martínez-Marín ◽  
Alberto Berjón ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Cancer Biology ◽  
Soft Tissues ◽  
Three Dimensional ◽  
3D Culture ◽  
Resistance Mechanisms ◽  
In Vitro Models ◽  
Tumour Spheroids ◽  
Current Therapies

Sarcomas are tumours of mesenchymal origin, which can arise in bone or soft tissues. They are rare but frequently quite aggressive and with a poor outcome. New approaches are needed to characterise these tumours and their resistance mechanisms to current therapies, responsible for tumour recurrence and treatment failure. This review is focused on the potential of three-dimensional (3D) in vitro models, including multicellular tumour spheroids (MCTS) and organoids, and the latest data about their utility for the study on important properties for tumour development. The use of spheroids as a particularly valuable alternative for compound high throughput screening (HTS) in different areas of cancer biology is also discussed, which enables the identification of new therapeutic opportunities in commonly resistant tumours.

scholarly journals In vitro models of fetal lung development to enhance research into congenital lung diseases

2021 ◽  
Author(s):  
Soichi Shibuya ◽  
Jessica Allen-Hyttinen ◽  
Paolo De Coppi ◽  
Federica Michielin
Keyword(s):  
Lung Development ◽  
Lung Diseases ◽  
Ex Vivo ◽  
Fetal Lung ◽  
Branching Morphogenesis ◽  
In Vitro Models ◽  
Normal Lung ◽  
Novel Therapeutic Strategies ◽  
Pseudoglandular Stage

Abstract Purpose This paper aims to build upon previous work to definitively establish in vitro models of murine pseudoglandular stage lung development. These can be easily translated to human fetal lung samples to allow the investigation of lung development in physiologic and pathologic conditions. Methods Lungs were harvested from mouse embryos at E12.5 and cultured in three different settings, i.e., whole lung culture, mesenchyme-free epithelium culture, and organoid culture. For the whole lung culture, extracted lungs were embedded in Matrigel and incubated on permeable filters. Separately, distal epithelial tips were isolated by firstly removing mesothelial and mesenchymal cells, and then severing the tips from the airway tubes. These were then cultured either in branch-promoting or self-renewing conditions. Results Cultured whole lungs underwent branching morphogenesis similarly to native lungs. Real-time qPCR analysis demonstrated expression of key genes essential for lung bud formation. The culture condition for epithelial tips was optimized by testing different concentrations of FGF10 and CHIR99021 and evaluating branching formation. The epithelial rudiments in self-renewing conditions formed spherical 3D structures with homogeneous Sox9 expression. Conclusion We report efficient protocols for ex vivo culture systems of pseudoglandular stage mouse embryonic lungs. These models can be applied to human samples and could be useful to paediatric surgeons to investigate normal lung development, understand the pathogenesis of congenital lung diseases, and explore novel therapeutic strategies.

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 State of the art on lung organoids in mammals

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Fabienne Archer ◽  
Alexandra Bobet-Erny ◽  
Maryline Gomes
Keyword(s):  
Lung Development ◽  
One Health ◽  
State Of The Art ◽  
Animal Health ◽  
In Vitro Models ◽  
Cancer Genetic ◽  
3 Dimensional ◽  
The One ◽  
Species Specific

AbstractThe number and severity of diseases affecting lung development and adult respiratory function have stimulated great interest in developing new in vitro models to study lung in different species. Recent breakthroughs in 3-dimensional (3D) organoid cultures have led to new physiological in vitro models that better mimic the lung than conventional 2D cultures. Lung organoids simulate multiple aspects of the real organ, making them promising and useful models for studying organ development, function and disease (infection, cancer, genetic disease). Due to their dynamics in culture, they can serve as a sustainable source of functional cells (biobanking) and be manipulated genetically. Given the differences between species regarding developmental kinetics, the maturation of the lung at birth, the distribution of the different cell populations along the respiratory tract and species barriers for infectious diseases, there is a need for species-specific lung models capable of mimicking mammal lungs as they are of great interest for animal health and production, following the One Health approach. This paper reviews the latest developments in the growing field of lung organoids.

scholarly journals Beyond 3D culture models of cancer

2015 ◽  
Vol 7 (283) ◽  
pp. 283ps9-283ps9 ◽  
Author(s):  
Kandice Tanner ◽  
Michael M. Gottesman
Keyword(s):  
In Vitro Culture ◽  
Three Dimensional ◽  
3D Culture ◽  
Drug Efficacy ◽  
Spatiotemporal Evolution ◽  
Culture Models ◽  
Dynamic Interplay

The mechanisms underlying the spatiotemporal evolution of tumor ecosystems present a challenge in evaluating drug efficacy. In this Perspective, we address the use of three-dimensional in vitro culture models to delineate the dynamic interplay between the tumor and the host microenvironment in an effort to attain realistic platforms for assessing pharmaceutical efficacy in patients.

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