scholarly journals Advanced Multi-Dimensional Cellular Models as Emerging Reality to Reproduce In Vitro the Human Body Complexity

2021 ◽  
Vol 22 (3) ◽  
pp. 1195
Author(s):  
Giada Bassi ◽  
Maria Aurora Grimaudo ◽  
Silvia Panseri ◽  
Monica Montesi
Keyword(s):  
Three Dimensional ◽  
Chemical Properties ◽  
Basic Research ◽  
Biomedical Science ◽  
Specific Cell ◽  
Multicellular Spheroids ◽  
Physiological Models ◽  
Cellular Models

A hot topic in biomedical science is the implementation of more predictive in vitro models of human tissues to significantly improve the knowledge of physiological or pathological process, drugs discovery and screening. Bidimensional (2D) culture systems still represent good high-throughput options for basic research. Unfortunately, these systems are not able to recapitulate the in vivo three-dimensional (3D) environment of native tissues, resulting in a poor in vitro–in vivo translation. In addition, intra-species differences limited the use of animal data for predicting human responses, increasing in vivo preclinical failures and ethical concerns. Dealing with these challenges, in vitro 3D technological approaches were recently bioengineered as promising platforms able to closely capture the complexity of in vivo normal/pathological tissues. Potentially, such systems could resemble tissue-specific extracellular matrix (ECM), cell–cell and cell–ECM interactions and specific cell biological responses to mechanical and physical/chemical properties of the matrix. In this context, this review presents the state of the art of the most advanced progresses of the last years. A special attention to the emerging technologies for the development of human 3D disease-relevant and physiological models, varying from cell self-assembly (i.e., multicellular spheroids and organoids) to the use of biomaterials and microfluidic devices has been given.

Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Biological Research ◽  
Specific Gene ◽  
Specific Cell ◽  
Organotypic Cultures ◽  
Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

scholarly journals The Revolutionary Roads to Study Cell–Cell Interactions in 3D In Vitro Pancreatic Cancer Models

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 930
Author(s):  
Donatella Delle Cave ◽  
Riccardo Rizzo ◽  
Bruno Sainz ◽  
Giuseppe Gigli ◽  
Loretta L. del Mercato ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Response ◽  
Three Dimensional ◽  
Cellular Models ◽  
Common Cancer ◽  
Cancer Models ◽  
Anti Cancer ◽  
Tumor Environment

Pancreatic cancer, the fourth most common cancer worldwide, shows a highly unsuccessful therapeutic response. In the last 10 years, neither important advancements nor new therapeutic strategies have significantly impacted patient survival, highlighting the need to pursue new avenues for drug development discovery and design. Advanced cellular models, resembling as much as possible the original in vivo tumor environment, may be more successful in predicting the efficacy of future anti-cancer candidates in clinical trials. In this review, we discuss novel bioengineered platforms for anticancer drug discovery in pancreatic cancer, from traditional two-dimensional models to innovative three-dimensional ones.

Three-dimensional Growth of Renal Epithelial Cells in Vitro: A Tool in Toxicity Testing

1993 ◽  
Vol 21 (2) ◽  
pp. 191-195 ◽  
Author(s):  
Knut-Jan Andersen ◽  
Erik Ilsø Christensen ◽  
Hogne Vik
Keyword(s):  
Epithelial Cells ◽  
Three Dimensional ◽  
Toxicity Testing ◽  
Renal Tissue ◽  
Epithelial Cell Line ◽  
Multicellular Spheroids ◽  
Renal Epithelial Cell ◽  
Renal Epithelial Cells

The tissue culture of multicellular spheroids from the renal epithelial cell line LLC-PK1 (proximal tubule) is described. This represents a biological system of intermediate complexity between renal tissue in vivo and simple monolayer cultures. The multicellular structures, which show many similarities to kidney tubules in vivo, including a vectorial water transport, should prove useful for studying the potential nephrotoxicity of drugs and chemicals in vitro. In addition, the propagation of renal epithelial cells as multicellular spheroids in serum-free culture may provide information on the release of specific biological parameters, which may be suppressed or masked in serum-supplemented media.

scholarly journals Organoid based personalized medicine: from bench to bedside

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Yaqi Li ◽  
Peiyuan Tang ◽  
Sanjun Cai ◽  
Junjie Peng ◽  
Guoqiang Hua
Keyword(s):  
Stem Cells ◽  
Personalized Medicine ◽  
Adult Stem Cells ◽  
Three Dimensional ◽  
Basic Research ◽  
Normal Tissues ◽  
Technology Applications ◽  
Genetically Manipulated

AbstractThree-dimensional cultured organoids have become a powerful in vitro research tool that preserves genetic, phenotypic and behavioral trait of in vivo organs, which can be established from both pluripotent stem cells and adult stem cells. Organoids derived from adult stem cells can be established directly from diseased epithelium and matched normal tissues, and organoids can also be genetically manipulated by CRISPR-Cas9 technology. Applications of organoids in basic research involve the modeling of human development and diseases, including genetic, infectious and malignant diseases. Importantly, accumulating evidence suggests that biobanks of patient-derived organoids for many cancers and cystic fibrosis have great value for drug development and personalized medicine. In addition, organoids hold promise for regenerative medicine. In the present review, we discuss the applications of organoids in the basic and translational research.

scholarly journals Recent Advances in Three-Dimensional Multicellular Spheroid Culture and Future Development

Micromachines ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 96
Author(s):  
Honglin Shen ◽  
Shuxiang Cai ◽  
Chuanxiang Wu ◽  
Wenguang Yang ◽  
Haibo Yu ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Multicellular Spheroids ◽  
Three Dimensional Model ◽  
Advantages And Disadvantages ◽  
High Throughput Drug Screening ◽  
Tumor Research ◽  
Basic Biology ◽  
And Function

Three-dimensional multicellular spheroids (MCSs) have received extensive attention in the field of biomedicine due to their ability to simulate the structure and function of tissues in vivo more accurately than traditional in vitro two-dimensional models and to simulate cell–cell and cell extracellular matrix (ECM) interactions. It has become an important in vitro three-dimensional model for tumor research, high-throughput drug screening, tissue engineering, and basic biology research. In the review, we first summarize methods for MCSs generation and their respective advantages and disadvantages and highlight the advances of hydrogel and microfluidic systems in the generation of spheroids. Then, we look at the application of MCSs in cancer research and other aspects. Finally, we discuss the development direction and prospects of MCSs

scholarly journals Graphene Coated Scaffold for Bone Tissue Engineering: Physicochemical and Osteogenic Characterizations

2021 ◽  
Author(s):  
Sajad Bahrami ◽  
Nafiseh Baheiraei ◽  
Mostafa Shahrezaee
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue ◽  
Three Dimensional ◽  
Chemical Properties ◽  
Cranial Bone ◽  
Drying Methods ◽  
Porous Scaffolds ◽  
Alizarin Red

Abstract Variety of bone-related diseases and injures and limitations of traditional regeneration methods need to introduce new tissue substitutes. Tissue engineering and regeneration combined with nanomedicine can provide different natural or synthetic and combined scaffolds with bone mimicking properties for implant in the injured area. In this study, we synthesized collagen (Col) and reduced graphene oxide coated collagen (Col-rGO) scaffolds and evaluated their in vitro and in vivo effects on bone tissue repair. Col and Col-rGO scaffolds were synthesized by chemical crosslinking and freeze-drying methods. The surface topography, mechanical and chemical properties of scaffolds were characterized and showed three-dimensional (3D) porous scaffolds and successful coating of rGO on Col. rGO coating enhanced mechanical strength of Col-rGO scaffolds compared with Col scaffolds by 2.8 folds. Furthermore, Col-rGO scaffolds confirmed that graphene addition not only did not any cytotoxic effects but also enhanced human bone marrow-derived mesenchymal stem cells (hBMSCs) viability and proliferation with 3D adherence and expansion. Finally, scaffolds implantation into rabbit cranial bone defect for 12 weeks showed increased bone formation, confirmed by Hematoxylin-Eosin (H&E) and alizarin red staining. Altogether, the study showed that rGO coating improves Col scaffold properties and could be a promising implant for bone injuries.

scholarly journals Computationally going where experiments cannot: a dynamical assessment of dendritic ion channel currents during in vivo-like states

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 180 ◽  
Author(s):  
Alexandre Guet-McCreight ◽  
Frances K. Skinner
Keyword(s):  
Ion Channel ◽  
Contextual Information ◽  
Computational Modelling ◽  
Signal Propagation ◽  
Specific Cell ◽  
Cellular Models ◽  
Channel Current ◽  
Channel Currents

Background: Despite technological advances, how specific cell types are involved in brain function remains shrouded in mystery. Further, little is known about the contribution of different ion channel currents to cell excitability across different neuronal subtypes and their dendritic compartments in vivo. The picture that we do have is largely based on somatic recordings performed in vitro. Uncovering dendritic ion channel current contributions in neuron subtypes that represent a minority of the neuronal population is not currently a feasible task using purely experimental means. Methods: We employ two morphologically-detailed multi-compartment models of a specific type of inhibitory interneuron, the oriens lacunosum moleculare (OLM) cell. The OLM cell is a well-studied cell type in CA1 hippocampus that is important in gating sensory and contextual information. We create in vivo-like states for these cellular models by including levels of synaptic bombardment that would occur in vivo. Using visualization tools and analyses we assess the ion channel current contribution profile across the different somatic and dendritic compartments of the models. Results: We identify changes in dendritic excitability, ion channel current contributions and co-activation patterns between in vitro and in vivo-like states. Primarily, we find that the relative timing between ion channel currents are mostly invariant between states, but exhibit changes in magnitudes and decreased propagation across dendritic compartments. We also find enhanced dendritic hyperpolarization-activated cyclic nucleotide-gated channel (h-channel) activation during in vivo-like states, which suggests that dendritically located h-channels are functionally important in altering signal propagation in the behaving animal. Conclusions: Overall, we have demonstrated, using computational modelling, the dynamical changes that can occur to ion channel mechanisms governing neuronal spiking. Simultaneous access to dendritic compartments during simulated in vivo states shows that the magnitudes of some ion channel current contributions are differentially altered during in vivo-like states relative to in vitro.

scholarly journals Advances in multicellular spheroids formation

2017 ◽  
Vol 14 (127) ◽  
pp. 20160877 ◽  
Author(s):  
X. Cui ◽  
Y. Hartanto ◽  
H. Zhang
Keyword(s):  
Three Dimensional ◽  
Confined Space ◽  
Multicellular Spheroids ◽  
Fundamental Building Block ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions ◽  
Cell Cell

Three-dimensional multicellular spheroids (MCSs) have a complex architectural structure, dynamic cell–cell/cell–matrix interactions and bio-mimicking in vivo microenvironment. As a fundamental building block for tissue reconstruction, MCSs have emerged as a powerful tool to narrow down the gap between the in vitro and in vivo model. In this review paper, we discussed the structure and biology of MCSs and detailed fabricating methods. Among these methods, the approach in microfluidics with hydrogel support for MCS formation is promising because it allows essential cell–cell/cell–matrix interactions in a confined space.

scholarly journals Heterotypic Multicellular Spheroids as Experimental and Preclinical Models of Sprouting Angiogenesis

Biology ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 18
Author(s):  
Igor V. Vakhrushev ◽  
Elizaveta K. Nezhurina ◽  
Pavel A. Karalkin ◽  
Anastasia V. Tsvetkova ◽  
Nataliya S. Sergeeva ◽  
...  
Keyword(s):  
Drug Testing ◽  
Molecular Mechanisms ◽  
Basic Research ◽  
Experimental Models ◽  
Multicellular Spheroids ◽  
Preclinical Research ◽  
Sprouting Angiogenesis ◽  
Essential Components

Sprouting angiogenesis is the common response of live tissues to physiological and pathological angiogenic stimuli. Its accurate evaluation is of utmost importance for basic research and practical medicine and pharmacology and requires adequate experimental models. A variety of assays for angiogenesis were developed, none of them perfect. In vitro approaches are generally less physiologically relevant due to the omission of essential components regulating the process. However, only in vitro models can be entirely non-xenogeneic. The limitations of the in vitro angiogenesis assays can be partially overcome using 3D models mimicking tissue O2 and nutrient gradients, the influence of the extracellular matrix (ECM), and enabling cell-cell interactions. Here we present a review of the existing models of sprouting angiogenesis that are based on the use of endothelial cells (ECs) co-cultured with perivascular or other stromal cells. This approach provides an excellent in vitro platform for further decoding of the cellular and molecular mechanisms of sprouting angiogenesis under conditions close to the in vivo conditions, as well as for preclinical drug testing and preclinical research in tissue engineering and regenerative medicine.

scholarly journals Recent Advances in Three-Dimensional Multicellular Spheroid Formation for Biomedical Research

2020 ◽  
Vol 63 (6) ◽  
pp. 245-251
Author(s):  
Jae Hong Park
Keyword(s):  
Functional Performance ◽  
Three Dimensional ◽  
Basic Mechanism ◽  
In Vivo Model ◽  
Multicellular Spheroid ◽  
Multicellular Spheroids ◽  
Recent Advances ◽  
Structural And Functional Properties

Multicellular spheroids (MCSs) from three dimensional culture, which is a complex architectural structure with dynamic cell to cell and cell to matrix interactions, mimic real tissues regarding structural and functional properties. MCSs have emerged as an effective tool for filling up the gap between the in vitro and in vivo experimental model and can replace the in vivo model. The viability and functional performance can be enhanced when cells are grown as multicellular spheroid (MCS). In this review paper, we discussed the basic mechanism of MCS formation, their biomedical applications, and recent advances in MCS culture and tissue engineering.

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