scholarly journals To Better Generate Organoids, What Can We Learn From Teratomas?

2021 ◽  
Vol 9 ◽  
Author(s):  
Hongyu Li ◽  
Lixiong Gao ◽  
Jinlin Du ◽  
Tianju Ma ◽  
Zi Ye ◽  
...  
Keyword(s):  
Animal Models ◽  
Disease Modeling ◽  
3D Culture ◽  
Cellular Heterogeneity ◽  
Developmental Studies ◽  
Genomic Profile ◽  
Organization Studies ◽  
Culture Systems

The genomic profile of animal models is not completely matched with the genomic profile of humans, and 2D cultures do not represent the cellular heterogeneity and tissue architecture found in tissues of their origin. Derived from 3D culture systems, organoids establish a crucial bridge between 2D cell cultures and in vivo animal models. Organoids have wide and promising applications in developmental research, disease modeling, drug screening, precision therapy, and regenerative medicine. However, current organoids represent only single or partial components of a tissue, which lack blood vessels, native microenvironment, communication with near tissues, and a continuous dorsal-ventral axis within 3D culture systems. Although efforts have been made to solve these problems, unfortunately, there is no ideal method. Teratoma, which has been frequently studied in pathological conditions, was recently discovered as a new in vivo model for developmental studies. In contrast to organoids, teratomas have vascularized 3D structures and regions of complex tissue-like organization. Studies have demonstrated that teratomas can be used to mimic multilineage human development, enrich specific somatic progenitor/stem cells, and even generate brain organoids. These results provide unique opportunities to promote our understanding of the vascularization and maturation of organoids. In this review, we first summarize the basic characteristics, applications, and limitations of both organoids and teratomas and further discuss the possibility that in vivo teratoma systems can be used to promote the vascularization and maturation of organoids within an in vitro 3D culture system.

Abstract 1717: Circulating tumor cells from in vitro 3D culture systems have tumor-initiating capacity in vivo

2016 ◽  
Author(s):  
Marina C. Cabrera ◽  
Elaine Hurt ◽  
Xiaoru Chen ◽  
Shi Xiaoqing ◽  
Haifeng Bao
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
3D Culture ◽  
Culture Systems

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 Bioengineered 3D Glial Cell Culture Systems and Applications for Neurodegeneration and Neuroinflammation

2017 ◽  
Vol 22 (5) ◽  
pp. 583-601 ◽  
Author(s):  
P. Marc D. Watson ◽  
Edel Kavanagh ◽  
Gary Allenby ◽  
Matthew Vassey
Keyword(s):  
Cell Culture ◽  
Drug Discovery ◽  
Glial Cell ◽  
Critical Role ◽  
3D Culture ◽  
Cell Types ◽  
Culture Systems ◽  
Cellular Environment

Neurodegeneration and neuroinflammation are key features in a range of chronic central nervous system (CNS) diseases such as Alzheimer’s and Parkinson’s disease, as well as acute conditions like stroke and traumatic brain injury, for which there remains significant unmet clinical need. It is now well recognized that current cell culture methodologies are limited in their ability to recapitulate the cellular environment that is present in vivo, and there is a growing body of evidence to show that three-dimensional (3D) culture systems represent a more physiologically accurate model than traditional two-dimensional (2D) cultures. Given the complexity of the environment from which cells originate, and their various cell–cell and cell–matrix interactions, it is important to develop models that can be controlled and reproducible for drug discovery. 3D cell models have now been developed for almost all CNS cell types, including neurons, astrocytes, microglia, and oligodendrocyte cells. This review will highlight a number of current and emerging techniques for the culture of astrocytes and microglia, glial cell types with a critical role in neurodegenerative and neuroinflammatory conditions. We describe recent advances in glial cell culture using electrospun polymers and hydrogel macromolecules, and highlight how these novel culture environments influence astrocyte and microglial phenotypes in vitro, as compared to traditional 2D systems. These models will be explored to illuminate current trends in the techniques used to create 3D environments for application in research and drug discovery focused on astrocytes and microglial cells.

scholarly journals In vitro and Animal Models for Antiviral Therapy in Papillomavirus Infections

1997 ◽  
Vol 8 (5) ◽  
pp. 381-400 ◽  
Author(s):  
MA Stanley ◽  
PJ Masterson ◽  
PK Nicholls
Keyword(s):  
Animal Models ◽  
Viral Gene Expression ◽  
Chemotherapeutic Agents ◽  
Viral Gene ◽  
Published Data ◽  
Papillomavirus Infections ◽  
Culture Systems ◽  
Species Specific

The need for antiviral therapies for papillomavirus infections is well recognized but the difficulties of reproducing the infectious cycle of papillomaviruses in vitro has hindered our understanding of virus-cell interactions and the regulation of viral gene expression during permissive growth. Recent advances in understanding the temporal expression and function of papillomavirus proteins has enabled consideration of a targeted approach to papillomavirus chemotherapy and in particular the inhibition of viral replication by targeting the E1 and E2 proteins. There are in vitro culture systems available for the screening of new chemotherapeutic agents, since significant advances have been made with culture systems which promote epithelial differentiation in vitro. However, to date, there are no published data which show that virions generated in vitro can infect keratinocytes and initiate another round of replication in vitro. In vivo animal models are therefore necessary to assess the efficacy of antivirals in preventing and treating viral infection, particularly for the low-risk genital viruses which are on the whole refractory to culture in vitro. Although papillomaviruses affect a wide variety of hosts in a species-specific manner, the animals most useful for modelling papillomavirus infections include the rabbit, ox, mouse, dog, horse, primate and sheep. The ideal animal model should be widely available, easy to house and handle, be large enough to allow for adequate tissue sampling, develop lesions on anatomical sites comparable with those in human diseases and these lesions should be readily accessible for monitoring and ideally should yield large amounts of infectious virus particles for use in both in vivo and in vitro studies. The relative merits of the various papillomavirus animal models available in relation to these criteria are discussed.

scholarly journals Collagen hydrogel confinement of amyloid-β accelerates aggregation and reduces cytotoxic effects

2019 ◽  
Author(s):  
Laura W. Simpson ◽  
Gregory L. Szeto ◽  
Hacene Boukari ◽  
Theresa A. Good ◽  
Jennie B. Leach
Keyword(s):  
3D Culture ◽  
Amyloid Β ◽  
Correlation Spectroscopy ◽  
Great Promise ◽  
Culture Systems ◽  
Glass Substrates ◽  
Collagen Hydrogel ◽  
Β Sheet

AbstractAlzheimer’s disease (AD) is the most common form of dementia and is associated with the accumulation of amyloid-β (Aβ), a peptide whose aggregation has been associated with neurotoxicity. Drugs targeting Aβ have shown great promise in 2D in vitro models and mouse models, yet preclinical and clinical trials for AD have been highly disappointing. We propose that current in vitro culture systems for discovering and developing AD drugs have significant limitations; specifically, that Aβ aggregation is vastly different in these 2D cultures carried out on flat plastic or glass substrates vs. in a 3D environment, such as brain tissue, where Aβ confinement very likely alters aggregation kinetics and thermodynamics. In this work, we identified attenuation of Aβ cytotoxicity in 3D hydrogel culture compared to 2D cell culture. We investigated Aβ structure and aggregation in solution vs. hydrogel using Transmission Electron Microscopy (TEM), Fluorescence Correlation Spectroscopy (FCS), and Thioflavin T (ThT) assays. Our results reveal that the equilibrium is shifted to stable β-sheet aggregates in hydrogels and away from the relatively unstable/unstructured presumed toxic oligomeric Aβ species in solution. Volume exclusion imparted by hydrogel confinement stabilizes unfolded, presumably toxic species, promoting stable extended β-sheet fibrils. These results, taken together with the many recent reports that 3D hydrogel cell cultures enable cell morphologies and epigenetic changes that are more similar to cells in vivo compared to 2D cultures, strongly suggest that AD drugs should be tested in 3D culture systems as a step along the development pathway towards new, more effective therapeutics.

scholarly journals Hydrogel based tissue engineering and its future applications in personalized disease modeling and regenerative therapy

2022 ◽  
Vol 11 (1) ◽  
Author(s):  
Shikha Chaudhary ◽  
Eliza Chakraborty
Keyword(s):  
Tissue Engineering ◽  
Drug Discovery ◽  
Animal Models ◽  
Disease Modeling ◽  
3D Culture ◽  
Clinical Applications ◽  
Cancer Drug ◽  
Main Body ◽  
Organoid Culture

Abstract Background Evolution in the in vitro cell culture from conventional 2D to 3D technique has been a significant accomplishment. The 3D culture models have provided a close and better insight into the physiological study of the human body. The increasing demand for organs like liver, kidney, and pancreas for transplantation, rapid anti-cancer drug screening, and the limitations associated with the use of animal models have attracted the interest of researchers to explore 3D organ culture. Main body Natural, synthetic, and hybrid material-based hydrogels are being used as scaffolds in 3D culture and provide 'close-to-in vivo’ structures. Organoids: the stem cell-derived small size 3D culture systems are now favored due to their ability to mimic the in-vivo conditions of organ or tissue and this characteristic has made it eligible for a variety of clinical applications, drug discovery and regenerative medicine are a few of the many areas of application. The use of animal models for clinical applications has been a long-time ethical and biological challenge to get accurate outcomes. 3D bioprinting has resolved the issue of vascularization in organoid culture to a great extent by its layer-by-layer construction approach. The 3D bioprinted organoids have a popular application in personalized disease modeling and rapid drug development and therapeutics. Short conclusions This review paper, focuses on discussing the novel organoid culture approach, its advantages and limitations, and potential applications in a variety of life science areas namely cancer research, cell therapy, tissue engineering, and personalized medicine and drug discovery. Graphical Abstract

scholarly journals Retinal Organ Cultures as Alternative Research Models

2019 ◽  
Vol 47 (1) ◽  
pp. 19-29 ◽  
Author(s):  
Sven Schnichels ◽  
Tobias Kiebler ◽  
José Hurst ◽  
Ana M. Maliha ◽  
Marina Löscher ◽  
...  
Keyword(s):  
Animal Models ◽  
Organ Culture ◽  
Ex Vivo ◽  
Organ Cultures ◽  
Culture Systems ◽  
Cellular Processes ◽  
Experimental Systems ◽  
Vessel Morphology

Ex vivo organ cultures represent unique research models, as they combine the advantages of cell cultures with those of animal models. Being able to mimic in vivo situations through the use of organ cultures provides an excellent opportunity to investigate cellular processes, molecular pathways and cell–cell interactions, as well as structural and synaptic organisation. Human and animal organ cultures are now well established and comprise sensitive, easy-to-manipulate experimental systems that raise minimal ethical concerns. The eye, in particular, is a very complex organ that is not easy to reproduce in vitro. However, a lot of research has been dedicated to the development of suitable ocular organ cultures. This review covers the various ex vivo retinal organ culture systems available for use in ophthalmology research and compares them with commonly used animal models. In particular, bovine and porcine retinal organ culture systems are described, because the size, anatomy, physiology and vessel morphology of bovine and porcine eyes are similar to the human eye in an undisputed way, thus making them good models. In addition, these animals are widely used by the food industry and the eyes are considered surplus material. A short overview of murine, rat, rabbit, cat, canine and simian retinal organ cultures is also provided.

Brain-on-a-chip Devices for Drug Screening and Disease Modeling Applications

2019 ◽  
Vol 24 (45) ◽  
pp. 5419-5436 ◽  
Author(s):  
Beatrice Miccoli ◽  
Dries Braeken ◽  
Yi-Chen Ethan Li
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Drug Screening ◽  
Disease Modeling ◽  
New Drugs ◽  
Screening Process ◽  
Pharmacological Screening ◽  
The Brain

:Neurodegenerative disorders are related to the progressive functional loss of the brain, often connected to emotional and physical disability and, ultimately, to death. These disorders, strongly connected to the aging process, are becoming increasingly more relevant due to the increase of life expectancy. Current pharmaceutical treatments poorly tackle these diseases, mainly acting only on their symptomology. One of the main reasons of this is the current drug development process, which is not only expensive and time-consuming but, also, still strongly relies on animal models at the preclinical stage.:Organ-on-a-chip platforms have the potential to strongly impact and improve the drug screening process by recreating in vitro the functionality of human organs. Patient-derived neurons from different regions of the brain can be directly grown and differentiated on a brain-on-a-chip device where the disease development, progression and pharmacological treatments can be studied and monitored in real time. The model reliability is strongly improved by using human-derived cells, more relevant than animal models for pharmacological screening and disease monitoring. The selected cells will be then capable of proliferating and organizing themselves in the in vivo environment thanks to the device architecture, materials selection and bio-chemical functionalization.:In this review, we start by presenting the fundamental strategies adopted for brain-on-a-chip devices fabrication including e.g., photolithography, micromachining and 3D printing technology. Then, we discuss the state-of-theart of brain-on-a-chip platforms including their role in the study of the functional architecture of the brain e.g., blood-brain barrier, or of the most diffuse neurodegenerative diseases like Alzheimer’s and Parkinson’s. At last, the current limitations and future perspectives of this approach for the development of new drugs and neurodegenerative diseases modeling will be discussed.

scholarly journals Self-Assembling Peptide Hydrogels - PeptiGels® as a Platform for Hepatic Organoid Culture

2021 ◽  
Author(s):  
Adedamola Olayanju ◽  
Aline F Miller ◽  
Tahera Ansari ◽  
Christopher E. Goldring
Keyword(s):  
Ex Vivo ◽  
3D Culture ◽  
Molecular Techniques ◽  
3 Dimensional ◽  
Culture Systems ◽  
Self Assembling ◽  
Technological Platform ◽  
Peptide Hydrogels

AbstractA major challenge in advancing preclinical studies is the lack of robust in vitro culture systems that fully recapitulate the in vivo scenario together with limited clinical translational to humans. Organoids, as 3-dimensional (3D) self-replicating structures are increasingly being shown as powerful models for ex vivo experimentation in the field of regenerative medicine and drug discovery. Organoid formation requires the use of extracellular matrix (ECM) components to provide a 3D platform. However, the most commonly used ECM, essential for maintaining organoid growth is Matrigel and is derived from a tumorigenic source which limits its translational ability. PeptiGels® which are self-assembling peptide hydrogels present as alternatives to traditional ECM for use in 3D culture systems. Synthetic PeptiGels® are non-toxic, biocompatible, biodegradable and can be tuneable to simulate different tissue microenvironments. In this study, we validated the use of different types of PeptiGels® for porcine hepatic organoid growth. Hepatic organoids were assessed morphologically and using molecular techniques to determine the optimum PeptiGel® formulation. The outcome clearly demonstrated the ability of PeptiGel® to support organoid growth and offer themselves as a technological platform for 3D cultured physiologically and clinically relevant data.

scholarly journals From Clones to Buds and Branches: The Use of Lung Organoids to Model Branching Morphogenesis Ex Vivo

2021 ◽  
Vol 9 ◽  
Author(s):  
Ana Ivonne Vazquez-Armendariz ◽  
Susanne Herold
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
3D Culture ◽  
Cell Types ◽  
Branching Morphogenesis ◽  
Cell Fate Decisions ◽  
Culture Systems

Three-dimensional (3D) organoid culture systems have rapidly emerged as powerful tools to study organ development and disease. The lung is a complex and highly specialized organ that comprises more than 40 cell types that offer several region-specific roles. During organogenesis, the lung goes through sequential and morphologically distinctive stages to assume its mature form, both structurally and functionally. As branching takes place, multipotent epithelial progenitors at the distal tips of the growing/bifurcating epithelial tubes progressively become lineage-restricted, giving rise to more differentiated and specialized cell types. Although many cellular and molecular mechanisms leading to branching morphogenesis have been explored, deeper understanding of biological processes governing cell-fate decisions and lung patterning is still needed. Given that these distinct processes cannot be easily analyzedin vivo, 3D culture systems have become a valuable platform to study organogenesisin vitro. This minireview focuses on the current lung organoid systems that recapitulate developmental events occurring before and during branching morphogenesis. In addition, we also discuss their limitations and future directions.

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