scholarly journals Artificial Tumor Microenvironments in Neuroblastoma

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1629
Author(s):  
Colin H. Quinn ◽  
Andee M. Beierle ◽  
Elizabeth A. Beierle
Keyword(s):  
Extracellular Matrix ◽  
Three Dimensional ◽  
Therapeutic Interventions ◽  
3D Bioprinting ◽  
Culture Studies ◽  
In Vivo Models ◽  
Novel Treatments ◽  
Tumor Microenvironments ◽  
Novel Approach

In the quest to advance neuroblastoma therapeutics, there is a need to have a deeper understanding of the tumor microenvironment (TME). From extracellular matrix proteins to tumor associated macrophages, the TME is a robust and diverse network functioning in symbiosis with the solid tumor. Herein, we review the major components of the TME including the extracellular matrix, cytokines, immune cells, and vasculature that support a more aggressive neuroblastoma phenotype and encumber current therapeutic interventions. Contemporary treatments for neuroblastoma are the result of traditional two-dimensional culture studies and in vivo models that have been translated to clinical trials. These pre-clinical studies are costly, time consuming, and neglect the study of cofounding factors such as the contributions of the TME. Three-dimensional (3D) bioprinting has become a novel approach to studying adult cancers and is just now incorporating portions of the TME and advancing to study pediatric solid. We review the methods of 3D bioprinting, how researchers have included TME pieces into the prints, and highlight present studies using neuroblastoma. Ultimately, incorporating the elements of the TME that affect neuroblastoma responses to therapy will improve the development of innovative and novel treatments. The use of 3D bioprinting to achieve this aim will prove useful in developing optimal therapies for children with neuroblastoma.

scholarly journals Three-dimensional in situ morphometrics of Mycobacterium tuberculosis infection within lesions by optical mesoscopy and novel acid-fast staining

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Robert J. Francis ◽  
Gillian Robb ◽  
Lee McCann ◽  
Bhagwati Khatri ◽  
James Keeble ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Three Dimensional ◽  
Large Field ◽  
Staining Procedure ◽  
3D Analysis ◽  
Mycobacterium Tuberculosis Infection ◽  
In Vivo Models ◽  
Novel Approach

AbstractTuberculosis (TB) preclinical testing relies on in vivo models including the mouse aerosol challenge model. The only method of determining colony morphometrics of TB infection in a tissue in situ is two-dimensional (2D) histopathology. 2D measurements consider heterogeneity within a single observable section but not above and below, which could contain critical information. Here we describe a novel approach, using optical clearing and a novel staining procedure with confocal microscopy and mesoscopy, for three-dimensional (3D) measurement of TB infection within lesions at sub-cellular resolution over a large field of view. We show TB morphometrics can be determined within lesion pathology, and differences in infection with different strains of Mycobacterium tuberculosis. Mesoscopy combined with the novel CUBIC Acid-Fast (CAF) staining procedure enables a quantitative approach to measure TB infection and allows 3D analysis of infection, providing a framework which could be used in the analysis of TB infection in situ.

scholarly journals Of balls, inks and cages: Hybrid biofabrication of 3D tissue analogs

2018 ◽  
Vol 5 (1) ◽  
Author(s):  
Nicanor Moldovan ◽  
Leni Maldovan ◽  
Michael Raghunath
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Hybrid Approach ◽  
Three Dimensional ◽  
3D Bioprinting ◽  
Support Structures ◽  
Cell Clusters ◽  
3D Space ◽  
Technical Solutions

The overarching principle of three-dimensional (3D) bioprinting is the placing of cells or cell clusters in the 3D space to generate a cohesive tissue microarchitecture that comes close to in vivo characteristics. To achieve this goal, several technical solutions are available, generating considerable combinatorial bandwidth: (i) Support structures are generated first, and cells are seeded subsequently; (ii) alternatively, cells are delivered in a printing medium, so-called “bioink,” that contains them during the printing process and ensures shape fidelity of the generated structure; and (iii) a “scaffold-free” version of bioprinting, where only cells are used and the extracellular matrix is produced by the cells themselves, also recently entered a phase of accelerated development and successful applications. However, the scaffold-free approaches may still benefit from secondary incorporation of scaffolding materials, thus expanding their versatility. Reversibly, the bioink-based bioprinting could also be improved by adopting some of the principles and practices of scaffold-free biofabrication. Collectively, we anticipate that combinations of these complementary methods in a “hybrid” approach, rather than their development in separate technological niches, will largely increase their efficiency and applicability in tissue engineering.

Induction of in Vivo Ectopic Hematopoiesis by a Three-Dimensional Structured Extracellular Matrix Derived from Decellularized Cancellous Bone

2019 ◽  
Vol 5 (11) ◽  
pp. 5669-5680 ◽  
Author(s):  
Naoko Nakamura ◽  
Tsuyoshi Kimura ◽  
Kwangwoo Nam ◽  
Toshiya Fujisato ◽  
Hiroo Iwata ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cancellous Bone ◽  
Three Dimensional

scholarly journals Using Spheroids as Building Blocks Towards 3D Bioprinting of Tumor Microenvironment

2021 ◽  
Vol 7 (4) ◽  
pp. 444
Author(s):  
Pei Zhuang ◽  
Yi-Hua Chiang ◽  
Maria Serafim Fernanda ◽  
Mei He
Keyword(s):  
Tumor Microenvironment ◽  
Prediction Models ◽  
Three Dimensional ◽  
3D Culture ◽  
Building Blocks ◽  
3D Bioprinting ◽  
Multicellular Spheroids ◽  
Tumor Models ◽  
3D Printed

Cancer still ranks as a leading cause of mortality worldwide. Although considerable efforts have been dedicated to anticancer therapeutics, progress is still slow, partially due to the absence of robust prediction models. Multicellular tumor spheroids, as a major three-dimensional (3D) culture model exhibiting features of avascular tumors, gained great popularity in pathophysiological studies and high throughput drug screening. However, limited control over cellular and structural organization is still the key challenge in achieving in vivo like tissue microenvironment. 3D bioprinting has made great strides toward tissue/organ mimicry, due to its outstanding spatial control through combining both cells and materials, scalability, and reproducibility. Prospectively, harnessing the power from both 3D bioprinting and multicellular spheroids would likely generate more faithful tumor models and advance our understanding on the mechanism of tumor progression. In this review, the emerging concept on using spheroids as a building block in 3D bioprinting for tumor modeling is illustrated. We begin by describing the context of the tumor microenvironment, followed by an introduction of various methodologies for tumor spheroid formation, with their specific merits and drawbacks. Thereafter, we present an overview of existing 3D printed tumor models using spheroids as a focus. We provide a compilation of the contemporary literature sources and summarize the overall advancements in technology and possibilities of using spheroids as building blocks in 3D printed tissue modeling, with a particular emphasis on tumor models. Future outlooks about the wonderous advancements of integrated 3D spheroidal printing conclude this review.

scholarly journals Bio-inks for 3D bioprinting: recent advances and future prospects

2017 ◽  
Vol 8 (31) ◽  
pp. 4451-4471 ◽  
Author(s):  
Ilze Donderwinkel ◽  
Jan C. M. van Hest ◽  
Neil R. Cameron
Keyword(s):  
Extracellular Matrix ◽  
Three Dimensional ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Cell Aggregates ◽  
3D Bioprinting ◽  
Future Prospects ◽  
Printing Inks ◽  
Polymer Bead ◽  
Polymeric Hydrogels

In the last decade, interest in the field of three-dimensional (3D) bioprinting has increased enormously. This review describes all the currently used bio-printing inks, including polymeric hydrogels, polymer bead microcarriers, cell aggregates and extracellular matrix proteins.

Interaction between vascular endothelial cells and vascular intimal spindle-shaped cells in vitro

1983 ◽  
Vol 60 (1) ◽  
pp. 89-102
Author(s):  
D de Bono ◽  
C. Green
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Three Dimensional ◽  
Vascular Endothelial ◽  
Pure Cultures ◽  
Species Specific ◽  
Endothelial Growth Factor

The interactions between human or bovine vascular endothelial cells and fibroblast-like vascular intimal spindle-shaped cells have been studied in vitro, using species-specific antibodies to identify the different components in mixed cultures. Pure cultures of endothelial cells grow as uniform, nonoverlapping monolayers, but this growth pattern is lost after the addition of spindle cells, probably because the extracellular matrix secreted by the latter causes the endothelial cells to modify the way they are attached to the substrate. The result is a network of tubular aggregates of endothelial cells in a three-dimensional ‘polylayer’ of spindle-shaped cells. On the other hand, endothelial cells added to growth-inhibited cultures of spindle-shaped cells will grow in sheets over the surface of the culture. Human endothelial cells grown in contact with spindle-shaped cells have a reduced requirement for a brain-derived endothelial growth factor. The interactions of endothelial cells and other connective tissue cells in vitro may be relevant to the mechanisms of endothelial growth and blood vessel formation in vivo, and emphasize the potential importance of extracellular matrix in controlling endothelial cell behaviour.

scholarly journals Biophysical studies of protein misfolding and aggregation in in vivo models of Alzheimer's and Parkinson's diseases

2020 ◽  
Vol 53 ◽  
Author(s):  
Tessa Sinnige ◽  
Karen Stroobants ◽  
Christopher M. Dobson ◽  
Michele Vendruscolo
Keyword(s):  
Protein Misfolding ◽  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Therapeutic Interventions ◽  
In Vivo Models ◽  
Disease Modifying Drugs ◽  
Parkinson’S Diseases ◽  
Protein Misfolding And Aggregation

Abstract Neurodegenerative disorders, including Alzheimer's (AD) and Parkinson's diseases (PD), are characterised by the formation of aberrant assemblies of misfolded proteins. The discovery of disease-modifying drugs for these disorders is challenging, in part because we still have a limited understanding of their molecular origins. In this review, we discuss how biophysical approaches can help explain the formation of the aberrant conformational states of proteins whose neurotoxic effects underlie these diseases. We discuss in particular models based on the transgenic expression of amyloid-β (Aβ) and tau in AD, and α-synuclein in PD. Because biophysical methods have enabled an accurate quantification and a detailed understanding of the molecular mechanisms underlying protein misfolding and aggregation in vitro, we expect that the further development of these methods to probe directly the corresponding mechanisms in vivo will open effective routes for diagnostic and therapeutic interventions.

scholarly journals Fabrication of 3D Printing Scaffold with Porcine Skin Decellularized Bio-Ink for Soft Tissue Engineering

Materials ◽  
2020 ◽  
Vol 13 (16) ◽  
pp. 3522
Author(s):  
Su Jeong Lee ◽  
Jun Hee Lee ◽  
Jisun Park ◽  
Wan Doo Kim ◽  
Su A Park
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
3D Printing ◽  
Three Dimensional ◽  
3D Bioprinting ◽  
Research Groups ◽  
Porcine Skin ◽  
Alginate Hydrogel ◽  
Chemical Treatments ◽  
Soft Tissue Engineering

Recently, many research groups have investigated three-dimensional (3D) bioprinting techniques for tissue engineering and regenerative medicine. The bio-ink used in 3D bioprinting is typically a combination of synthetic and natural materials. In this study, we prepared bio-ink containing porcine skin powder (PSP) to determine rheological properties, biocompatibility, and extracellular matrix (ECM) formation in cells in PSP-ink after 3D printing. PSP was extracted without cells by mechanical, enzymatic, and chemical treatments of porcine dermis tissue. Our developed PSP-containing bio-ink showed enhanced printability and biocompatibility. To identify whether the bio-ink was printable, the viscosity of bio-ink and alginate hydrogel was analyzed with different concentration of PSP. As the PSP concentration increased, viscosity also increased. To assess the biocompatibility of the PSP-containing bio-ink, cells mixed with bio-ink printed structures were measured using a live/dead assay and WST-1 assay. Nearly no dead cells were observed in the structure containing 10 mg/mL PSP-ink, indicating that the amounts of PSP-ink used were nontoxic. In conclusion, the proposed skin dermis decellularized bio-ink is a candidate for 3D bioprinting.

scholarly journals Gut organoids: mini-tissues in culture to study intestinal physiology and disease

2019 ◽  
Vol 317 (3) ◽  
pp. C405-C419 ◽  
Author(s):  
Mohammad Almeqdadi ◽  
Miyeko D. Mana ◽  
Jatin Roper ◽  
Ömer H. Yilmaz
Keyword(s):  
Cell Lines ◽  
Three Dimensional ◽  
Gastrointestinal Diseases ◽  
In Vivo Models ◽  
Intestinal Physiology ◽  
Microbe Interactions ◽  
Immortalized Cell ◽  
In Vitro Cell Cultures

In vitro, cell cultures are essential tools in the study of intestinal function and disease. For the past few decades, monolayer cellular cultures, such as cancer cell lines or immortalized cell lines, have been widely applied in gastrointestinal research. Recently, the development of three-dimensional cultures known as organoids has permitted the growth of normal crypt-villus units that recapitulate many aspects of intestinal physiology. Organoid culturing has also been applied to study gastrointestinal diseases, intestinal-microbe interactions, and colorectal cancer. These models are amenable to CRISPR gene editing and drug treatments, including high-throughput small-molecule testing. Three-dimensional intestinal cultures have been transplanted into mice to develop versatile in vivo models of intestinal disease, particularly cancer. Limitations of currently available organoid models include cost and challenges in modeling nonepithelial intestinal cells, such as immune cells and the microbiota. Here, we describe the development of organoid models of intestinal biology and the applications of organoids for study of the pathophysiology of intestinal diseases and cancer.

scholarly journals Simple In-House Fabrication of Microwells for Generating Uniform Hepatic Multicellular Cancer Aggregates and Discovering Novel Therapeutics

Materials ◽  
2019 ◽  
Vol 12 (20) ◽  
pp. 3308 ◽  
Author(s):  
Chiao-Yi Chiu ◽  
Ying-Chi Chen ◽  
Kuang-Wei Wu ◽  
Wen-Chien Hsu ◽  
Hong-Ping Lin ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cell Viability ◽  
Near Infrared ◽  
Hollow Spheres ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Therapeutic Interventions ◽  
Therapeutic Modalities ◽  
Photothermal Treatment

Three-dimensional (3D) cell culture models have become powerful tools because they better simulate the in vivo pathophysiological microenvironment than traditional two-dimensional (2D) monolayer cultures. Tumor cells cultured in a 3D system as multicellular cancer aggregates (MCAs) recapitulate several critical in vivo characteristics that enable the study of biological functions and drug discovery. The microwell, in particular, has emerged as a revolutionary technology in the generation of MCAs as it provides geometrically defined microstructures for culturing size-controlled MCAs amenable for various downstream functional assays. This paper presents a simple and economical microwell fabrication methodology that can be conveniently incorporated into a conventional laboratory setting and used for the discovery of therapeutic interventions for liver cancer. The microwells were 400–700 µm in diameter, and hepatic MCAs (Huh-7 cells) were cultured in them for up to 5 days, over which time they grew to 250–520 µm with good viability and shape. The integrability of the microwell fabrication with a high-throughput workflow was demonstrated using a standard 96-well plate for proof-of-concept drug screening. The IC50 of doxorubicin was determined to be 9.3 µM under 2D conditions and 42.8 µM under 3D conditions. The application of photothermal treatment was demonstrated by optimizing concanavalin A-FITC conjugated silica-carbon hollow spheres (SCHSs) at a concentration of 500:200 µg/mL after a 2 h incubation to best bind with MCAs. Based on this concentration, which was appropriate for further photothermal treatment, the relative cell viability was assessed through exposure to a 3 W/cm2 near-infrared laser for 20 min. The relative fluorescence intensity showed an eight-fold reduction in cell viability, confirming the feasibility of using photothermal treatment as a potential therapeutic intervention. The proposed microwell integration is envisioned to serve as a simple in-house technique for the generation of MCAs useful for discovering therapeutic modalities for liver cancer treatment.

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