scholarly journals High-throughput acoustofluidic fabrication of tumor spheroids

Lab on a Chip ◽  
2019 ◽  
Vol 19 (10) ◽  
pp. 1755-1763 ◽  
Author(s):  
Bin Chen ◽  
Yue Wu ◽  
Zheng Ao ◽  
Hongwei Cai ◽  
Asael Nunez ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Response ◽  
Three Dimensional ◽  
3D Culture ◽  
Multicellular Spheroids ◽  
Tumor Spheroids

Three-dimensional (3D) culture of multicellular spheroids, offering a desirable biomimetic microenvironment, is appropriate for recapitulating tissue cellular adhesive complexity and revealing a more realistic drug response.

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 3D cell culture technology – a new insight into in vitro research – a review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Justyna Sośniak ◽  
Jolanta Opiela
Keyword(s):  
Three Dimensional ◽  
3D Culture ◽  
3D Cell Culture ◽  
2D Systems ◽  
Multicellular Spheroids ◽  
Advantages And Disadvantages ◽  
3D Cell Cultures ◽  
Culture Models ◽  
Culture Technology

Abstract Most in vitro cell-based research is based on two-dimensional (2D) systems where growth and development take place on a flat surface, which does not reflect the natural environment of the cells. The imperfection and limitations of culture in 2D systems eventually led to the creation of three-dimensional (3D) culture models that more closely reproduce the actual conditions of physiological cell growth. Since the inception of 3D culture technology, many culture models have been developed, such as technologies of multicellular spheroids, organoids, and organs on chips in the technology of scaffolding, hydrogels, bio-printing and liquid media. In this review we will focus on the advantages and disadvantages of the 2D vs. 3D cell cultures technologies. We will also try to sum up available 3D cultures systems and materials for building 3D scaffolds.

scholarly journals Novel three-dimensional cultures provide insights into thyroid cancer behavior

2020 ◽  
Vol 27 (2) ◽  
pp. 111-121 ◽  
Author(s):  
Mason A Lee ◽  
Kensey N Bergdorf ◽  
Courtney J Phifer ◽  
Caroline Y Jones ◽  
Sonia Y Byon ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
High Throughput ◽  
Drug Response ◽  
3D Culture ◽  
The United States ◽  
Cancer Cell Lines ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancer Cell Lines

Thyroid cancer has the fastest growing incidence of any cancer in the United States, as measured by the number of new cases per year. Despite advances in tissue culture techniques, a robust model for thyroid cancer spheroid culture is yet to be developed. Using eight established thyroid cancer cell lines, we created an efficient and cost-effective 3D culture system that can enhance our understanding of in vivo treatment response. We found that all eight cell lines readily form spheroids in culture with unique morphology, size, and cytoskeletal organization. In addition, we developed a high-throughput workflow that allows for drug screening of spheroids. Using this approach, we found that spheroids from K1 and TPC1 cells demonstrate significant differences in their sensitivities to dabrafenib treatment that closely model expected patient drug response. In addition, K1 spheroids have increased sensitivity to dabrafenib when compared to monolayer K1 cultures. Utilizing traditional 2D cultures of these cell lines, we evaluated the mechanisms of this drug response, showing dramatic and acute changes in their actin cytoskeleton as well as inhibition of migratory behavior in response to dabrafenib treatment. Our study is the first to describe the development of a robust spheroid system from established cultured thyroid cancer cell lines and adaptation to a high-throughput format. We show that combining 3D culture with traditional 2D methods provides a complementary and powerful approach to uncover drug sensitivity and mechanisms of inhibition in thyroid cancer.

scholarly journals Natural and Synthetic Biomaterials for Engineering Multicellular Tumor Spheroids

Polymers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 2506
Author(s):  
Advika Kamatar ◽  
Gokhan Gunay ◽  
Handan Acar
Keyword(s):  
Cancer Research ◽  
Three Dimensional ◽  
3D Culture ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
In Vivo Models ◽  
Advantages And Disadvantages ◽  
Natural And Synthetic

The lack of in vitro models that represent the native tumor microenvironment is a significant challenge for cancer research. Two-dimensional (2D) monolayer culture has long been the standard for in vitro cell-based studies. However, differences between 2D culture and the in vivo environment have led to poor translation of cancer research from in vitro to in vivo models, slowing the progress of the field. Recent advances in three-dimensional (3D) culture have improved the ability of in vitro culture to replicate in vivo conditions. Although 3D cultures still cannot achieve the complexity of the in vivo environment, they can still better replicate the cell–cell and cell–matrix interactions of solid tumors. Multicellular tumor spheroids (MCTS) are three-dimensional (3D) clusters of cells with tumor-like features such as oxygen gradients and drug resistance, and represent an important translational tool for cancer research. Accordingly, natural and synthetic polymers, including collagen, hyaluronic acid, Matrigel®, polyethylene glycol (PEG), alginate and chitosan, have been used to form and study MCTS for improved clinical translatability. This review evaluates the current state of biomaterial-based MCTS formation, including advantages and disadvantages of the different biomaterials and their recent applications to the field of cancer research, with a focus on the past five years.

scholarly journals A fully automated high-throughput workflow for 3D-based chemical screening in human midbrain organoids

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Henrik Renner ◽  
Martha Grabos ◽  
Katharina J Becker ◽  
Theresa E Kagermeier ◽  
Jie Wu ◽  
...  
Keyword(s):  
High Throughput ◽  
Three Dimensional ◽  
3D Culture ◽  
Drug Effects ◽  
Global Gene Expression ◽  
Automated Generation ◽  
Chemical Screening ◽  
Physiological Relevance ◽  
Composition And Structure ◽  
High Throughput Screens

Three-dimensional (3D) culture systems have fueled hopes to bring about the next generation of more physiologically relevant high-throughput screens (HTS). However, current protocols yield either complex but highly heterogeneous aggregates (‘organoids’) or 3D structures with less physiological relevance (‘spheroids’). Here, we present a scalable, HTS-compatible workflow for the automated generation, maintenance, and optical analysis of human midbrain organoids in standard 96-well-plates. The resulting organoids possess a highly homogeneous morphology, size, global gene expression, cellular composition, and structure. They present significant features of the human midbrain and display spontaneous aggregate-wide synchronized neural activity. By automating the entire workflow from generation to analysis, we enhance the intra- and inter-batch reproducibility as demonstrated via RNA sequencing and quantitative whole mount high-content imaging. This allows assessing drug effects at the single-cell level within a complex 3D cell environment in a fully automated HTS workflow.

scholarly journals High-throughput 3D screening for differentiation of hPSC-derived cell therapy candidates

2020 ◽  
Vol 6 (32) ◽  
pp. eaaz1457
Author(s):  
Riya Muckom ◽  
Xiaoping Bao ◽  
Eric Tran ◽  
Evelyn Chen ◽  
Abirami Murugappan ◽  
...  
Keyword(s):  
Cell Therapy ◽  
High Throughput ◽  
System Development ◽  
Three Dimensional ◽  
3D Culture ◽  
3D Cell Culture ◽  
Culture Conditions ◽  
Nervous System Development ◽  
Oligodendrocyte Progenitor Cells ◽  
Cell Therapies

The emergence of several cell therapy candidates in the clinic is an encouraging sign for human diseases/disorders that currently have no effective treatment; however, scalable production of these cell therapies has become a bottleneck. To overcome this barrier, three-dimensional (3D) cell culture strategies have been considered for enhanced cell production. Here, we demonstrate a high-throughput 3D culture platform used to systematically screen 1200 culture conditions with varying doses, durations, dynamics, and combinations of signaling cues to derive oligodendrocyte progenitor cells and midbrain dopaminergic neurons from human pluripotent stem cells (hPSCs). Statistical models of the robust dataset reveal previously unidentified patterns about cell competence to Wnt, retinoic acid, and sonic hedgehog signals, and their interactions, which may offer insights into the combinatorial roles these signals play in human central nervous system development. These insights can be harnessed to optimize production of hPSC-derived cell replacement therapies for a range of neurological indications.

scholarly journals Generation of High-Throughput Three-Dimensional Tumor Spheroids for Drug Screening

10.3791/57476 ◽  
2018 ◽  
Author(s):  
Lesley Mathews Griner ◽  
Kalyani Gampa ◽  
Toan Do ◽  
Huyen Nguyen ◽  
David Farley ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Three Dimensional ◽  
Tumor Spheroids

scholarly journals 3D spheroid models of paediatric SHH medulloblastoma mimic tumour biology, drug response and metastatic dissemination

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sophie J. Roper ◽  
Franziska Linke ◽  
Paul J. Scotting ◽  
Beth Coyle
Keyword(s):  
Drug Response ◽  
Three Dimensional ◽  
3D Culture ◽  
Cell Movement ◽  
Culture Method ◽  
Dual Inhibitor ◽  
Metastatic Dissemination ◽  
In Vitro Techniques

AbstractStudying medulloblastoma, the most common malignant paediatric brain tumour, requires simple yet realistic in vitro models. In this study, we optimised a robust, reliable, three-dimensional (3D) culture method for medulloblastoma able to recapitulate the spatial conformation, cell–cell and cell–matrix interactions that exist in vivo and in patient tumours. We show that, when grown under the same stem cell enriching conditions, SHH subgroup medulloblastoma cell lines established tight, highly reproducible 3D spheroids that could be maintained for weeks in culture and formed pathophysiological oxygen gradients. 3D spheroid culture also increased resistance to standard-of-care chemotherapeutic drugs compared to 2D monolayer culture. We exemplify how this model can enhance in vitro therapeutic screening approaches through dual-inhibitor studies and continual monitoring of drug response. Next, we investigated the initial stages of metastatic dissemination using brain-specific hyaluronan hydrogel matrices. RNA sequencing revealed downregulation of cell cycle genes and upregulation of cell movement genes and key fibronectin interactions in migrating cells. Analyses of these upregulated genes in patients showed that their expression correlated with early relapse and overall poor prognosis. Our 3D spheroid model is a significant improvement over current in vitro techniques, providing the medulloblastoma research community with a well-characterised and functionally relevant culture method.

Sign in / Sign up

Export Citation Format

Share Document