scholarly journals Recent Advances in Multicellular Tumor Spheroid Generation for Drug Screening

Biosensors ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 445
Author(s):  
Kwang-Ho Lee ◽  
Tae-Hyung Kim

Multicellular tumor spheroids (MCTs) have been employed in biomedical fields owing to their advantage in designing a three-dimensional (3D) solid tumor model. For controlling multicellular cancer spheroids, mimicking the tumor extracellular matrix (ECM) microenvironment is important to understand cell–cell and cell–matrix interactions. In drug cytotoxicity assessments, MCTs provide better mimicry of conventional solid tumors that can precisely represent anticancer drug candidates’ effects. To generate incubate multicellular spheroids, researchers have developed several 3D multicellular spheroid culture technologies to establish a research background and a platform using tumor modelingvia advanced materials science, and biosensing techniques for drug-screening. In application, drug screening was performed in both invasive and non-invasive manners, according to their impact on the spheroids. Here, we review the trend of 3D spheroid culture technology and culture platforms, and their combination with various biosensing techniques for drug screening in the biomedical field.

Author(s):  
Manashi Priyadarshini ◽  
Sibasish Mohanty ◽  
Tanushree Mahapatra ◽  
Pallavi Mohapatra ◽  
Rupesh Dash

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2747
Author(s):  
Li-Chi Chen ◽  
Hsin-Wen Wang ◽  
Chieh-Cheng Huang

Multicellular spheroids show three-dimensional (3D) organization with extensive cell–cell and cell–extracellular matrix interactions. Owing to their native tissue-mimicking characteristics, mesenchymal stem cell (MSC) spheroids are considered promising as implantable therapeutics for stem cell therapy. Herein, we aim to further enhance their therapeutic potential by tuning the cultivation parameters and thus the inherent niche of 3D MSC spheroids. Significantly increased expression of multiple pro-regenerative paracrine signaling molecules and immunomodulatory factors by MSCs was observed after optimizing the conditions for spheroid culture. Moreover, these alterations in cellular behaviors may be associated with not only the hypoxic niche developed in the spheroid core but also with the metabolic reconfiguration of MSCs. The present study provides efficient methods for manipulating the therapeutic capacity of 3D MSC spheroids, thus laying solid foundations for future development and clinical application of spheroid-based MSC therapy for regenerative medicine.


2017 ◽  
Vol 2 ◽  
pp. 136-144
Author(s):  
John Hughes

The analysis by microscopy of the compositions and microstructures of geomaterials found in historic structures and buildings is integral to archaeological, art-historical, conservation and restoration-related investigations, and supports decision making for material replacement and repair. In archaeology there is a need to elucidate past social, economic and technological processes, and to understand the environmental impacts of past human activities related to materials use. Standard light and electron microscopy are most commonly employed, but high resolution methods such as transmission electron and three-dimensional tomography such as µ-CT are also being used. Experimental and novel developments, where they overlap with advanced materials science, are uncommon. The application of scientific characterisation frames cultural heritage value, reinforcing our understanding of authenticity and integrity. Characterisation is constrained, in turn, by the values system that operates in cultural heritage. International charters and conservation philosophy necessitate the application of science to contextualising conservation. However, the appearance of science in heritage work has also led to the performance of science for its own sake (‘endoscience’, sensu Muñoz Viñas, Contemporary Theory of Conservation, Routledge, 2011). This moves some to suggest that there is a disconnect between scientific work and its practical value. Apparent communication problems between scientists applying microscopy and other stakeholders require changes to management of material characterisation in heritage projects.


2018 ◽  
Vol 7 (3) ◽  
pp. 181-190
Author(s):  
Parisa Pooyan ◽  
Luke P. Brewster ◽  
Rina Tannenbaum ◽  
Hamid Garmestani

Abstract As a rapidly growing area in materials design, the biomimetic approach at the frontier between biology and materials science aims to introduce advanced materials with structural diversities and functional versatilities by mimicking remarkable systems available in nature. Inspired by the fascinating nanostructured assembly existing in the cell walls of different plant species, we designed two fully bio-based green nanomaterials reinforced with renewable polysaccharide nanoparticles in the form of cellulose nanowhiskers (CNWs). In our initial design, the CNWs were incorporated into a cellulose acetate propionate matrix to form a bionanocomposite film, while in the second design the CNWs were entangled within a network of a collagenous medium to introduce a bionanocomposite hydrogel. Tensile and rheological measurements were carried out to study the system’s deformation as subjected to axial force or oscillatory shear. Biocompatibility was tested via incubation of human bone marrow-derived mesenchymal stem cells in vitro. Careful control of the processing conditions resulted in a three-dimensional rigid CNW network percolating within both biopolymer matrices, giving rise to an excellent performance at only a small fraction of CNWs at 3 wt.%. This study reveals that the fully bio-based green nanomaterials with enhanced mechanical percolation could construct a suitable platform for scaffolding in tissue engineering.


2015 ◽  
Vol 17 (2) ◽  
Author(s):  
Linfen Yu ◽  
Cynthia Ni ◽  
Samantha M. Grist ◽  
Carmen Bayly ◽  
Karen C. Cheung

1993 ◽  
Vol 21 (2) ◽  
pp. 191-195 ◽  
Author(s):  
Knut-Jan Andersen ◽  
Erik Ilsø Christensen ◽  
Hogne Vik

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.


2021 ◽  
Vol 22 (5) ◽  
pp. 2659
Author(s):  
Gianluca Costamagna ◽  
Giacomo Pietro Comi ◽  
Stefania Corti

In the last decade, different research groups in the academic setting have developed induced pluripotent stem cell-based protocols to generate three-dimensional, multicellular, neural organoids. Their use to model brain biology, early neural development, and human diseases has provided new insights into the pathophysiology of neuropsychiatric and neurological disorders, including microcephaly, autism, Parkinson’s disease, and Alzheimer’s disease. However, the adoption of organoid technology for large-scale drug screening in the industry has been hampered by challenges with reproducibility, scalability, and translatability to human disease. Potential technical solutions to expand their use in drug discovery pipelines include Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) to create isogenic models, single-cell RNA sequencing to characterize the model at a cellular level, and machine learning to analyze complex data sets. In addition, high-content imaging, automated liquid handling, and standardized assays represent other valuable tools toward this goal. Though several open issues still hamper the full implementation of the organoid technology outside academia, rapid progress in this field will help to prompt its translation toward large-scale drug screening for neurological disorders.


2021 ◽  
Vol 22 (6) ◽  
pp. 3019
Author(s):  
Naike Casagrande ◽  
Cinzia Borghese ◽  
Francesco Agostini ◽  
Cristina Durante ◽  
Mario Mazzucato ◽  
...  

A high platelet count is associated with a poor prognosis in ovarian cancer (OvCa). Despite good clinical responses with platinating agents in combination with taxanes, numerous OvCa patients relapse due to chemotherapy resistance. Here, we report that treatment of OvCa cells A2780, OVCAR5 and MDAH with releasate from activated platelets (PR) promoted multicellular tumor spheroid (MCTS) formation. These OvCa-MCTSs had increased percentages of CD133+ and aldehyde dehydrogenase (ALDH)+ cells, bona fide markers of OvCa cancer stem cells (CSCs). PR increased OVCAR5- and MDAH-MCTS viability and decreased the cytotoxic and pro-apoptotic effects of paclitaxel, cisplatin and carboplatin. PR increased the volume of spontaneously formed OVCAR8-MCTSs and counteracted their size reduction due to cisplatin, carboplatin and paclitaxel treatment. PR promoted the survival of ALDH+ and CD133+ OvCa cells during cisplatin, carboplatin and paclitaxel treatment. In conclusion, molecules and growth factors released by activated platelets (EGF, PDGF, TGF-β, IGF and CCL5) may protect tumor cells from chemotherapy by promoting the expansion of ALDH+ and CD133+ OvCa-CSCs, favoring drug resistance and tumor relapse.


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