Sulfobetaine polymers for effective permeability into multicellular tumor spheroids (MCTSs)

2022 ◽  
Author(s):  
Nobuyuki Morimoto ◽  
Keisuke Ota ◽  
Yuki Miura ◽  
Heungsoo Shin ◽  
Masaya Yamamoto
Keyword(s):  
Drug Screening ◽  
Effective Permeability ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
Tumor Tissues ◽  
Animal Tests

Multicellular tumor spheroids (MCTSs) are attractive for drug screening before animal tests because they emulate an in vivo microenvironment. The permeability of the MCTSs and tumor tissues by the candidate...

scholarly journals Encapsulated multicellular tumor spheroids as a novel in vitro model to study small size tumors

2003 ◽  
Vol 57 (12) ◽  
pp. 585-588 ◽  
Author(s):  
Elena Markvicheva ◽  
Lina Bezdetnaya ◽  
Artur Bartkowiak ◽  
Annie Marc ◽  
Jean-Louis Gorgen ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Tumor Biology ◽  
Cell Encapsulation ◽  
Large Cell ◽  
In Vitro Models ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
Vitro Model

Presently multicellular tumor spheroids (MTS) are being widely used in various aspects of tumor biology, including studies in biology and photodynamic therapy. The cellular organization of spheroids allows the recreation of in vivo small tumors much better than all common two-dimensional in vitro models. The cell encapsulation method could be proposed as a novel technique to quickly and easily prepare a large number of spheroids with narrow size distribution within a desirable diameter range. Moreover, the proposed technique for spheroid generation using encapsulated growing tumor cells could provide entirely new avenues to develop a novel spheroid co-culture model (for instance, the in vitro co-cultvation of tumor cells and monocytes, or epithelial cells, or fibroblasts etc). The current research was aimed at developing a simple and reliable method to encapsulate tumor cells and to cultivate them in vitro. In order to generate spheroids, MCF-7 cells were encapsulated and cultivated in 200 ml T-flasks in a 5% CO2 atmosphere at 37?C for 4-5 weeks. The cell proliferation was easily observed using a light microscope. The cells grew in aggregates increasing in size with time. The cell growth resulted in the formation of large cell clusters (spheroids) which filled the whole microcapsule volume in 4-5 weeks.

scholarly journals Confocal Microscopy in Conjunction With Haemocytometry to Evaluate the Imperative Physical Characteristics of Multicellular Tumor Spheroids

2021 ◽  
Author(s):  
Aziz UR RAHMAN
Keyword(s):  
Confocal Microscopy ◽  
Drug Uptake ◽  
Live Cells ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
Oriented Growth ◽  
Trypan Blue Exclusion ◽  
Trypan Blue Exclusion Method

Abstract Background: Tumor tissues resist penetration of therapeutic molecules. Multicellular tumor spheroids (MCTSs) were used as an in vitro tumor model. The aim of this study was to determine the growth of MCTSs with the age of spheroids, which could be applied and compared with in vivo drug uptake and penetration. Method: Spheroids were generated by liquid overlay techniques, and their diameter was measured by confocal microscopy for up to two weeks. The trypan blue exclusion method was used to count dead and live cells separately via a hemocytometer. Results: The pentaphysical characteristics of spheroids, including diameter, cell number, volume per cell, viability status, and estimated shell of viable and core of dead cells, were determined. The growth of spheroids was linear over the first week but declined in the 2nd week, which may be due to an overconcentration of dead cells and degraded products inside the spheroids, hence lowering the ratio of live cells in spheroids. Compaction of spheroids occurs from day 3 to day 7, with the mature spheroids having a low amount of extracellular space compared to intracellular volume. Conclusion: Age-oriented growth of MCTSs provides a rationale to predict less rapid penetration as spheroids get older and could be correlated with in vivo tumors to predict pharmaceutical and therapeutic intervention.

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.

Formation, Growth and Morphology of Multicellular Tumor Spheroids from a Human Colon Carcinoma Cell Line (LoVo)

1986 ◽  
Vol 72 (5) ◽  
pp. 459-467 ◽  
Author(s):  
Carla Soranzo ◽  
Gabriella Della Torre ◽  
Antonella Ingrosso
Keyword(s):  
Colon Carcinoma ◽  
Exponential Growth ◽  
Human Colon ◽  
Cell Ultrastructure ◽  
Exponential Growth Phase ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
Human Colon Carcinoma Cell ◽  
Human Colon Carcinoma

LoVo human colon carcinoma cells cultured by a liquid overlay technique form and grow as multicellular tumor spheroids. The growth curve of LoVo spheroids exhibits Gompertzian growth kinetics, i.e., exponential growth for 10 days, followed by exponential retardation in the rate of growth. Doubling time in the exponential growth phase is longer than in monolayer cultures (5 days for LoVo spheroids vs. 37 h for monolayers). When LoVo spheroids reach a diameter of about 300 ūm, a necrotic core appears in their center and continuously increases with spheroid growth. The cell ultrastructure and organization in spheroids closely resemble those of the same cells when grown as tumors in vivo or as monolayer, i.e. intestinal epithelium, desmosomes, intracytoplasmic lumina and acinar structures. Individual cells from spheroids can be obtained by trypsinization and assayed for colony formation. LoVo spheroids provide a model which can be readily manipulated and appears to be suitable for evaluation of anticancer drugs. A comparison of LoVo spheroids exposed to doxorubicin with the same cells grown in monolayers emphasized the role of cell organization in determining drug resistance.

scholarly journals Impact of multicellular tumor spheroids as an in vivo-like tumor model on anticancer drug response

2016 ◽  
Vol 48 (6) ◽  
pp. 2295-2302 ◽  
Author(s):  
BIANCA GALATEANU ◽  
ARIANA HUDITA ◽  
CAROLINA NEGREI ◽  
RODICA-MARIANA ION ◽  
MARIETA COSTACHE ◽  
...  
Keyword(s):  
Anticancer Drug ◽  
Drug Response ◽  
Tumor Model ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
Anticancer Drug Response

scholarly journals Generation of uniform-sized multicellular tumor spheroids using hydrogel microwells for advanced drug screening

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Jong Min Lee ◽  
Da Yeon Park ◽  
Letao Yang ◽  
Eun-Joong Kim ◽  
Christian D. Ahrberg ◽  
...  
Keyword(s):  
Drug Screening ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids

scholarly journals Stroma-Rich Co-Culture Multicellular Tumor Spheroids as a Tool for Photoactive Drugs Screening

2019 ◽  
Vol 8 (10) ◽  
pp. 1686 ◽  
Author(s):  
Ilya Yakavets ◽  
Samuel Jenard ◽  
Aurelie Francois ◽  
Yulia Maklygina ◽  
Victor Loschenov ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Indocyanine Green ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
High Throughput Screening ◽  
Chlorin E6 ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids

Conventional 3D multicellular tumor spheroids of head and neck squamous cell carcinoma (HNSCC) consisting exclusively of cancer cells have some limitations. They are compact cell aggregates that do not interact with their extracellular milieu, thus suffering from both insufficient extracellular matrix (ECM) deposition and absence of different types of stromal cells. In order to better mimic in vivo HNSCC tumor microenvironment, we have constructed a 3D stroma-rich in vitro model of HNSCC, using cancer-associated MeWo skin fibroblasts and FaDu pharynx squamous cell carcinoma. The expression of stromal components in heterospheroids was confirmed by immunochemical staining. The generated co-culture FaDu/MeWo spheroids were applied to study penetration, distribution and antitumor efficacy of photoactive drugs such as Temoporfin and Chlorin e6 used in the photodynamic therapy flow cytometry and fluorescence microscopy techniques. We also investigated the distribution of photodiagnostic agent Indocyanine Green. We demonstrated that the presence of stroma influences the behavior of photoactive drugs in different ways: (i) No effect on Indocyanine Green distribution; (ii) lower accumulation of Chlorin e6; (iii) better penetration and PDT efficiency of Temoporfin. Overall, the developed stroma-rich spheroids enlarge the arsenal of in vitro pre-clinical models for high-throughput screening of anti-cancer drugs.

Cancer-on-a-chip for Drug Screening

2019 ◽  
Vol 24 (45) ◽  
pp. 5407-5418 ◽  
Author(s):  
I-Chi Lee
Keyword(s):  
Clinical Trials ◽  
Drug Screening ◽  
Phase Iii ◽  
Preclinical Models ◽  
Micro Manufacturing ◽  
Matrix Deposition ◽  
Oncology Drug ◽  
Tumor Tissues ◽  
Manufacturing Technologies

: The oncology pharmaceutical research spent a shocking amount of money on target validation and drug optimization in preclinical models because many oncology drugs fail during clinical trial phase III. One of the most important reasons for oncology drug failures in clinical trials may due to the poor predictive tool of existing preclinical models. Therefore, in cancer research and personalized medicine field, it is critical to improve the effectiveness of preclinical predictions of the drug response of patients to therapies and to reduce costly failures in clinical trials. Three dimensional (3D) tumor models combine micro-manufacturing technologies mimic critical physiologic parameters present in vivo, including complex multicellular architecture with multicellular arrangement and extracellular matrix deposition, packed 3D structures with cell–cell interactions, such as tight junctions, barriers to mass transport of drugs, nutrients and other factors, which are similar to in vivo tumor tissues. These systems provide a solution to mimic the physiological environment for improving predictive accuracy in oncology drug discovery. : his review gives an overview of the innovations, development and limitations of different types of tumor-like construction techniques such as self-assemble spheroid formation, spheroids formation by micro-manufacturing technologies, micro-dissected tumor tissues and tumor organoid. Combination of 3D tumor-like construction and microfluidic techniques to achieve tumor on a chip for in vitro tumor environment modeling and drug screening were all included. Eventually, developmental directions and technical challenges in the research field are also discussed. We believe tumor on chip models have provided better sufficient clinical predictive power and will bridge the gap between proof-of-concept studies and a wider implementation within the oncology drug development for pathophysiological applications.

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