scholarly journals 3D Culture Systems for Exploring Cancer Immunology

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 56
Author(s):  
Allison A. Fitzgerald ◽  
Eric Li ◽  
Louis M. Weiner
Keyword(s):  
Immune Cell ◽  
Three Dimensional ◽  
3D Culture ◽  
3D Models ◽  
Therapeutic Benefit ◽  
Cancer Immunology ◽  
Microfluidic Chips ◽  
Murine Models ◽  
Human Immune System ◽  
Culture Systems

Cancer immunotherapy has revolutionized cancer treatment, spurring extensive investigation into cancer immunology and how to exploit this biology for therapeutic benefit. Current methods to investigate cancer-immune cell interactions and develop novel drug therapies rely on either two-dimensional (2D) culture systems or murine models. However, three-dimensional (3D) culture systems provide a potentially superior alternative model to both 2D and murine approaches. As opposed to 2D models, 3D models are more physiologically relevant and better replicate tumor complexities. Compared to murine models, 3D models are cheaper, faster, and can study the human immune system. In this review, we discuss the most common 3D culture systems—spheroids, organoids, and microfluidic chips—and detail how these systems have advanced our understanding of cancer immunology.

scholarly journals Extending In-Plane Impedance Measurements from 2D to 3D Cultures: Design Considerations

2021 ◽  
Vol 8 (1) ◽  
pp. 11
Author(s):  
Sorel E. De Leon ◽  
Lana Cleuren ◽  
Zay Yar Oo ◽  
Paul R. Stoddart ◽  
Sally L. McArthur
Keyword(s):  
Three Dimensional ◽  
3D Culture ◽  
Collagen Gel ◽  
Impedance Measurement ◽  
Impedance Spectrum ◽  
3D Models ◽  
Low Frequencies ◽  
3D Cell Cultures ◽  
3D Collagen ◽  
2D And 3D

Three-dimensional (3D) cell cultures have recently emerged as tools for biologically modelling the human body. As 3D models make their way into laboratories there is a need to develop characterisation techniques that are sensitive enough to monitor the cells in real time and without the need for chemical labels. Impedance spectroscopy has been shown to address both of these challenges, but there has been little research into the full impedance spectrum and how the different components of the system affect the impedance signal. Here we investigate the impedance of human fibroblast cells in 2D and 3D collagen gel cultures across a broad range of frequencies (10 Hz to 5 MHz) using a commercial well with in-plane electrodes. At low frequencies in both 2D and 3D models it was observed that protein adsorption influences the magnitude of the impedance for the cell-free samples. This effect was eliminated once cells were introduced to the systems. Cell proliferation could be monitored in 2D at intermediate frequencies (30 kHz). However, the in-plane electrodes were unable to detect any changes in the impedance at any frequency when the cells were cultured in the 3D collagen gel. The results suggest that in designing impedance measurement devices, both the nature and distribution of the cells within the 3D culture as well as the architecture of the electrodes are key variables.

A rhabdomyosarcoma hydrogel model to unveil cell-extracellular matrix interactions

2021 ◽  
Author(s):  
Mattia Saggioro ◽  
Stefania D'Agostino ◽  
Anna Gallo ◽  
Sara Crotti ◽  
Sara D'Aronco ◽  
...  
Keyword(s):  
Cell Culture ◽  
Extracellular Matrix ◽  
Three Dimensional ◽  
3D Culture ◽  
3D Cell Culture ◽  
Culture Systems ◽  
Matrix Interactions ◽  
In Vitro Systems ◽  
Extracellular Matrix Interactions

Three-dimensional (3D) culture systems are progressively getting attention given their potential in overcoming limitations of the classical 2D in vitro systems. Among different supports for 3D cell culture, hydrogels (HGs)...

scholarly journals Inhibitors of A Disintegrin And Metalloproteinases-10 reduce Hodgkin lymphoma cell growth in 3D microenvironments and enhance brentuximab-vedotin effect

Haematologica ◽  
2021 ◽  
Author(s):  
Roberta Pece ◽  
Sara Tavella ◽  
Delfina Costa ◽  
Serena Varesano ◽  
Caterina Camodeca ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Drug Testing ◽  
Cell Damage ◽  
Three Dimensional ◽  
3D Culture ◽  
Glucose Consumption ◽  
3D Models ◽  
Brentuximab Vedotin ◽  
Collagen Scaffolds ◽  
Antibody Drug Conjugate

Shedding of A Disintegrin And Metalloproteinases (ADAM10) substrates, like TNFα or CD30, can affect both anti-tumor immune response and antibody-drug-conjugate (ADC)-based immunotherapy. We have published two new ADAM10 inhibitors, LT4 and MN8 able to prevent such shedding in Hodgkin lymphoma (HL). Since tumor tissue architecture deeply influence the outcome of anti-cancer treatments, we set up new three-dimensional (3D) culture systemsto verify whether ADAM10 inhibitors can contribute to, or enhance, the anti-lymphoma effects of the ADC brentuximab-vedotin (BtxVed).To recapitulate some aspects of lymphoma structure and architecture, we assembled two 3D culture models: mixed spheroids made of HL lymph node (LN) mesenchymal stromal cells (MSC) and Reed Sternberg/Hodgkin lymphoma cells (HL cells) or collagen scaffolds repopulated with LN-MSC and HL cells. In these 3D systems we found that: 1) the ADAM10 inhibitors LT4 and MN8 reduce ATP content or glucose consumption, related to cell proliferation, increasing lactate dehydrogenase (LDH) release as a cell damage hallmark; 2) these events are paralleled by mixed spheroids size reduction and inhibition of CD30 and TNFα shedding; 3) the effects observed can be reproduced in repopulated HL LN-derived matrix or collagen scaffolds; 4) ADAM10 inhibitors enhance the antilymphoma effect of the anti-CD30 ADC BtxVed both in conventional cultures and in repopulated scaffolds. Thus, we provide evidence for direct and combined anti-lymphoma effect of ADAM10 inhibitors with BtxVed, leading to improvement of ADC effects; this is documented in 3D models recapitulating features of LN microenvironment, that can be proposed as reliable tool for antilymphoma drug testing.

scholarly journals 3D Culture as a Clinically Relevant Model for Personalized Medicine

2017 ◽  
Vol 22 (3) ◽  
pp. 245-253 ◽  
Author(s):  
Eliza Li Shan Fong ◽  
Tan Boon Toh ◽  
Hanry Yu ◽  
Edward Kai-Hua Chow
Keyword(s):  
Cancer Research ◽  
Drug Development ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Three Dimensional ◽  
3D Culture ◽  
Research Field ◽  
Cancer Drug ◽  
Specific Patient ◽  
Culture Systems

Advances in understanding many of the fundamental mechanisms of cancer progression have led to the development of molecular targeted therapies. While molecular targeted therapeutics continue to improve the outcome for cancer patients, tumor heterogeneity among patients, as well as intratumoral heterogeneity, limits the efficacy of these drugs to specific patient subtypes, as well as contributes to relapse. Thus, there is a need for a more personalized approach toward drug development and diagnosis that takes into account the diversity of cancer patients, as well as the complex milieu of tumor cells within a single patient. Three-dimensional (3D) culture systems paired with patient-derived xenografts or patient-derived organoids may provide a more clinically relevant system to address issues presented by personalized or precision medical approaches. In this review, we cover the current methods available for applying 3D culture systems toward personalized cancer research and drug development, as well as key challenges that must be addressed in order to fully realize the potential of 3D patient-derived culture systems for cancer drug development. Greater implementation of 3D patient-derived culture systems in the cancer research field should accelerate the development of truly personalized medical therapies for cancer patients.

500 USING THREE-DIMENSIONAL (3D) CULTURE SYSTEMS TO DELINEATE THE ROLE OF RANKL IN METASTATIC PROSTATE CANCER

2013 ◽  
Vol 189 (4S) ◽  
Author(s):  
Shabnam Ziaee ◽  
Shirly Sieh ◽  
Gina C-Y. Chu ◽  
Ruoxiang Wang ◽  
Dietmar Hutmacher ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Three Dimensional ◽  
3D Culture ◽  
Culture Systems

scholarly journals Effect of NMDA Receptor Agonist and Antagonist on Spermatogonia Stem Cells Proliferation in 2- and 3- Dimensional Culture Systems

2021 ◽  
Author(s):  
Amir Hessam Eskafi Noghani ◽  
Reza Asadpour ◽  
Adel Saberivand ◽  
Zohreh Mazaheri ◽  
Gholamreza Hamidian
Keyword(s):  
Flow Cytometry ◽  
Glutamic Acid ◽  
Three Dimensional ◽  
3D Culture ◽  
Enzymatic Digestion ◽  
Control Group ◽  
Two Dimensional ◽  
Culture Systems ◽  
Protein Levels ◽  
Proliferation Capacity

Abstract The main purpose of this study was to investigate the effect of D-serine (DS) and Dizocilpine (MK-801or Mk) on the proliferation of SSCs in two-dimensional (2D) and three-dimensional (3D) culture systems. The SSCs of male NMRI mice were isolated by enzymatic digestion and cultured for two weeks. Then, the identity of SSCs was confirmed by anti-Plzf and anti-GFR-α1 antibodies via immunocytochemistry (ICC). The proliferation capacity of SSCs was evaluated by their culture on a layer of the decellularized testicular matrix (DTM) prepared from mouse testis, as well as two-dimensional (2D) with different mediums. After two weeks of the initiation of proliferation culture on 3D and 2D medium, the pre-meiotic at the mRNA and protein levels were evaluated via qRT-PCR and flow cytometry methods, respectively. The results showed that the proliferation rate of SSCs in three-dimensional culture with 50 mM glutamic acid and 20 mM D-serine was significantly different from other groups after 14 days treatment. mRNA expression levels of Plzf in 3D-cultures supplemented by 20 mM D-serine and 50 mM glutamic acid were considerably higher than the 3D control group (p<0.001). The flow cytometry analysis revealed that the amount of Plzf in the 2D-culture groups of SSCs with 20mM MK-801 was considerably lower compared to the 2D-culture control group (p<0.001). This study indicated that decellularized testicular matrix supplemented with D-serine and glutamic acid could be considered a promising vehicle to support cells and provide an appropriate niche for the proliferation of SSCs.

scholarly journals Constitutive Activation of STAT3 in Myeloma Cells Cultured in a Three-Dimensional, Reconstructed Bone Marrow Model

2018 ◽  
Author(s):  
Yung-Hsing Huang ◽  
Ommoleila Molavi ◽  
Abdulraheem Alshareef ◽  
Moinul Haque ◽  
Qian Wang ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Single Cells ◽  
Active Form ◽  
Three Dimensional ◽  
3D Culture ◽  
3D Models ◽  
Oligonucleotide Array ◽  
Conventional Culture ◽  
3D Culture Model ◽  
Cells Cultured

Malignant cells cultured in three-dimensional (3D) models have been found to be phenotypically and biochemically different from their counterparts cultured conventionally. Since most of these studies employed solid cancers, how 3D culture affects multiple myeloma (MM) cells is not well understood. Here, we compared MM cells (U266 and RPMI8226) in a 3D culture model with those in conventional culture. While the conventionally cultured cells were present in single cells or small clusters, MM-3D cells grew in large spheroids. We discovered that STAT3 was the pathway that was more activated in 3D in both cell lines. The active form of STAT3 (pSTAT3), being absent in MM cells cultured conventionally, became detectable after 1-2 days in 3D culture. This elevated pSTAT3 level was dependent on the 3D environment, since it disappeared after transferring to conventional culture. STAT3 inhibition using a pharmacological agent, Stattic, significantly decreased the cell viability of MM cells and sensitized them to bortezomib in 3D culture. Using an oligonucleotide array, we found that 3D culture significantly increased the expression of several known STAT3 downstream genes implicated in oncogenesis. Since most primary MM tumors are naturally STAT3-active, studies of MM in the 3D culture can generate results that are more representative of the disease.

A Framework for Optimizing High-Content Imaging of 3D Models for Drug Discovery

2020 ◽  
Vol 25 (7) ◽  
pp. 709-722
Author(s):  
Judith Wardwell-Swanson ◽  
Mahomi Suzuki ◽  
Karen G. Dowell ◽  
Manuela Bieri ◽  
Eva C. Thoma ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Throughput ◽  
High Throughput Screening ◽  
Immune Cell ◽  
Three Dimensional ◽  
Morphological Characteristics ◽  
Drug Efficacy ◽  
3D Models ◽  
Routine Practice ◽  
High Content Imaging

Three-dimensional (3D) spheroid models are rapidly gaining favor for drug discovery applications due to their improved morphological characteristics, cellular complexity, long lifespan in culture, and higher physiological relevance relative to two-dimensional (2D) cell culture models. High-content imaging (HCI) of 3D spheroid models has the potential to provide valuable information to help researchers untangle disease pathophysiology and assess novel therapies more effectively. The transition from 2D monolayer models to dense 3D spheroids in HCI applications is not trivial, however, and requires 3D-optimized protocols, instrumentation, and resources. Here, we discuss considerations for moving from 2D to 3D models and present a framework for HCI and analysis of 3D spheroid models in a drug discovery setting. We combined scaffold-free, multicellular spheroid models with scalable, automation-compatible plate technology enabling image-based applications ranging from high-throughput screening to more complex, lower-throughput microphysiological systems of organ networks. We used this framework in three case studies: investigation of lipid droplet accumulation in a human liver nonalcoholic steatohepatitis (NASH) model, real-time immune cell interactions in a multicellular 3D lung cancer model, and a high-throughput screening application using a 3D co-culture model of gastric carcinoma to assess dose-dependent drug efficacy and specificity. The results of these proof-of-concept studies demonstrate the potential for high-resolution image-based analysis of 3D spheroid models for drug discovery applications, and confirm that cell-level and temporal-spatial analyses that fully exploit multicellular features of spheroid models are not only possible but soon will be routine practice in drug discovery workflows.

Abstract 4997: Using three-dimensional (3D) culture systems to delineate the role of RANKL in metastatic prostate cancer.

2013 ◽  
Author(s):  
Shabnam Ziaee ◽  
Shirly Sieh ◽  
Chia-Yi Chu ◽  
Ruoxiang Wang ◽  
Dietmar W. Hutmacher ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Three Dimensional ◽  
3D Culture ◽  
Culture Systems

scholarly journals Development of Injectable Thermosensitive Chitosan-Based Hydrogels for Cell Encapsulation

2020 ◽  
Vol 10 (18) ◽  
pp. 6550 ◽  
Author(s):  
Antonella Stanzione ◽  
Alessandro Polini ◽  
Velia La Pesa ◽  
Alessandro Romano ◽  
Angelo Quattrini ◽  
...  
Keyword(s):  
Three Dimensional ◽  
3D Culture ◽  
Cell Encapsulation ◽  
Mechanical Stiffness ◽  
Culture Systems ◽  
Beneficial Effects ◽  
Physico Chemical ◽  
Hydrogen Carbonate ◽  
Biological Tests

The three-dimensional complexity of the native extracellular matrix (ECM) suggests switching from 2D to 3D culture systems for providing the cells with an architecture more similar to the physiological environment. Reproducing the three-dimensionality in vitro can guarantee beneficial effects in terms of cell growth, adhesion, proliferation, and/or their differentiation. Hydrogels have the same tailorable physico-chemical and biological characteristics as ECM materials. In this study, we propose a thermoresponsive chitosan-based hydrogel that gels thanks to the addition of organic and inorganic salt solutions (beta-glycerolphosphate and sodium hydrogen carbonate) and is suitable for cell encapsulation allowing obtaining 3D culture systems. Physico-chemical analyses showed that the hydrogel formulations jellify at physiological conditions (37 °C, pH 7.4), are stable in vitro up to three weeks, have high swelling ratios and mechanical stiffness suitable for cellular encapsulation. Moreover, preliminary biological tests underlined the pronounced biocompatibility of the system. Therefore, these chitosan-based hydrogels are proposed as valid biomaterials for cell encapsulation.

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