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1

Smith, J. Torquil, and H. Frank Morrison. "Approximating spheroid inductive responses using spheres." GEOPHYSICS 71, no. 2 (2006): G21—G25. http://dx.doi.org/10.1190/1.2187738.

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Spheroid responses are important as limiting cases when modeling inductive responses of isolated metallic objects such as unexploded military ordnance. The response of high-permeability ([Formula: see text] ≥ 50) conductive spheroids of moderate aspect ratios (0.25–4) to excitation by uniform magnetic fields in the axial or transverse direction is approximated by the response of spheres of appropriate diameters, of the same conductivity and permeability, with magnitude rescaled based on the differing volumes, dc magnetizations, and high-frequency limit responses of the spheres and modelled sph
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Pevná, Viktória, Mariana Máčajová, Andrej Hovan, et al. "Spheroidal Model of SKBR3 and U87MG Cancer Cells for Live Imaging of Caspase-3 during Apoptosis Induced by Singlet Oxygen in Photodynamic Therapy." Biomedicines 10, no. 9 (2022): 2141. http://dx.doi.org/10.3390/biomedicines10092141.

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Aspects related to the response of cells to photodynamic therapy (PDT) have been well studied in cell cultures, which often grow in monolayers. In this work, we propose a spheroidal model of U87MG and SKBR3 cells designed to mimic superficial tumor tissue, small spheroids (<500 µm) suitable for confocal fluorescence microscopy, and larger spheroids (>500 µm) that can be xenografted onto quail chorioallantoic membrane (CAM) to study the effects of PDT in real time. Hypericin was used as a model molecule for a hydrophobic photosensitizer that can produce singlet oxygen (1O2). 1O2 productio
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Bridges, Michael A., David C. Walker, Robert A. Harris, Bruce R. Wilson, and A. George F. Davidson. "Cultured human nasal epithelial multicellular spheroids: polar cyst-like model tissues." Biochemistry and Cell Biology 69, no. 2-3 (1991): 102–8. http://dx.doi.org/10.1139/o91-016.

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We report here a new readily cultured nonadherent hollow spheroidal epithelial tissue model: human nasal epithelial multicellular spheroids, prepared from brushings of human nasal epithelium in vivo. Although cultured cyst-like epithelial models developed from embryonic, transformed, or polypoid tissues have been reported previously, human nasal epithelial multicellular spheroids are derived from normal mature nontransformed human airway epithelial cells. In our studies, spheroids ranged in size from 50 to 700 μm diameter (averaging approximately 250 μm). Cells of the spheroid displayed morpho
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4

Pevna, Viktoria, Mariana Macajová, Andrej Hovan, et al. "Spheroidal Model of SKBR3 and U87MG Cancer Cells for Live Imaging of Caspase-3 during Apoptosis Induced by Singlet Oxygen in Photodynamic Therapy." Biomedicines 10, no. 9 (2022): 2141. https://doi.org/10.3390/biomedicines10092141.

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Aspects related to the response of cells to photodynamic therapy (PDT) have been well studied in cell cultures, which often grow in monolayers. In this work, we propose a spheroidal model of U87MG and SKBR3 cells designed to mimic superficial tumor tissue, small spheroids (<500 um) suitable for confocal fluorescence microscopy, and larger spheroids (>500 um) that can be xenografted onto quail chorioallantoic membrane (CAM) to study the effects of PDT in real time. Hypericin was used as a model molecule for a hydrophobic photosensitizer that can produce singlet oxygen
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5

LIN, SUNG-JAN, WEN-CHU HSIAO, CHIH-JUNG HSU, et al. "THE EFFECT OF SERUM CONCENTRATION ON THE SPHEROID FORMING ACTIVITY AND CELL GROWTH OF HUMAN MELANOCYTES ON CHITOSAN SURFACE." Biomedical Engineering: Applications, Basis and Communications 18, no. 01 (2006): 42–46. http://dx.doi.org/10.4015/s1016237206000099.

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We have developed a chitosan-based melanocyte patch to improve the drawbacks encountered in autologous melanocyte transplantation for vitiligo treatment by use of melanocyte suspension. Melanocytes spontaneously grow into three dimensional spheroids on chitosan-coated surface and melanocyte spheroids show a better survival in growth factor and serum-deprived condition. Hence, preculturing melanocytes into spheroids on chitosan surface can provide melanocytes a survival advantage in stringent conditions. Up to date, the mechanism of the melanocyte spheroid formation is not clear. It has been sh
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6

Cesarz, Zoe, and Kenichi Tamama. "Spheroid Culture of Mesenchymal Stem Cells." Stem Cells International 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/9176357.

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Compared with traditional 2D adherent cell culture, 3D spheroidal cell aggregates, or spheroids, are regarded as more physiological, and this technique has been exploited in the field of oncology, stem cell biology, and tissue engineering. Mesenchymal stem cells (MSCs) cultured in spheroids have enhanced anti-inflammatory, angiogenic, and tissue reparative/regenerative effects with improved cell survival after transplantation. Cytoskeletal reorganization and drastic changes in cell morphology in MSC spheroids indicate a major difference in mechanophysical properties compared with 2D culture. E
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7

Trufanova, Natalia, Oleh Trufanov, Galyna Bozhok, et al. "Hypothermic Storage of Mesenchymal Stromal Cell-based Spheroids at a Temperature of 22°C." Problems of Cryobiology and Cryomedicine 34, no. 3 (2024): 186–200. https://doi.org/10.15407/cryo34.03.186.

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Spheroids formed from mesenchymal stromal/stem cells (MSCs) provide optimal microenvironment for cell potential and stemmness support being also promising structures for relevant research models as well as cell therapies development. Practical application requires the development of effective methods for storing spheroids. Storage at ambient temperature (22°C) can be safer and more convenient for short term transportation of MSC-based spheroids. Herein we report that the spheroids formed by human adipose tissue-derived MSCs can be stored at ambient temperature (22°C) for up to 7 days with effi
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8

Kolendowski, Bart, Sylvia Cheng, Yudith Ramos Valdes, Trevor G. Shepherd, and Gabriel E. DiMattia. "Transcriptomic Analyses of Ovarian Clear Cell Carcinoma Spheroids Reveal Distinct Proliferative Phenotypes and Therapeutic Vulnerabilities." Cells 14, no. 11 (2025): 785. https://doi.org/10.3390/cells14110785.

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Cancer cell spheroids autonomously form in the ascites fluid and are considered a conduit for epithelial ovarian cancer metastasis within the peritoneal cavity. Spheroids are homotypic, avascular 3D structures that acquire resistance to anoikis to remain viable after cellular detachment. We used in vitro spheroid model systems to interrogate pathways critical for spheroid cell proliferation, distinct from those driving monolayer cancer cell proliferation. Using the 105C and KOC-7c human ovarian clear cell carcinoma (OCCC) cell lines, which have distinct proliferative phenotypes as spheroids bu
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9

Iyengar, T., and T. Radhika. "Stokes flow of an incompressible micropolar fluid past a porous spheroidal shell." Bulletin of the Polish Academy of Sciences: Technical Sciences 59, no. 1 (2011): 63–74. http://dx.doi.org/10.2478/v10175-011-0010-5.

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Stokes flow of an incompressible micropolar fluid past a porous spheroidal shellConsider a pair of confocal prolate spheroids S0and S1where S0is within S1. Let the spheroid S0be a solid and the annular region between S0and S1be porous. The present investigation deals with a flow of an incompressible micropolar fluid past S1with a uniform stream at infinity along the common axis of symmetry of the spheroids. The flow outside the spheroid S1is assumed to follow the linearized version of Eringen's micropolar fluid flow equations and the flow within the porous region is assumed to be governed by t
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10

Ueki, Noriko, and Ken-ichi Wakabayashi. "Detergent-extractedVolvoxmodel exhibits an anterior–posterior gradient in flagellar Ca2+sensitivity." Proceedings of the National Academy of Sciences 115, no. 5 (2018): E1061—E1068. http://dx.doi.org/10.1073/pnas.1715489115.

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Volvox rousseletiiis a multicellular spheroidal green alga containing ∼5,000 cells, each equipped with two flagella (cilia). This organism shows striking photobehavior without any known intercellular communication. To help understand how the behavior of flagella is regulated, we developed a method to extract the whole organism with detergent and reactivate its flagellar motility. Upon addition of ATP, demembranated flagella (axonemes) in the spheroids actively beat and the spheroids swam as if they were alive. Under Ca2+-free conditions, the axonemes assumed planar and asymmetrical waveforms a
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11

Murphy, Kaitlin C., Ben P. Hung, Stephen Browne-Bourne, et al. "Measurement of oxygen tension within mesenchymal stem cell spheroids." Journal of The Royal Society Interface 14, no. 127 (2017): 20160851. http://dx.doi.org/10.1098/rsif.2016.0851.

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Spheroids formed of mesenchymal stem cells (MSCs) exhibit increased cell survival and trophic factor secretion compared with dissociated MSCs, making them therapeutically advantageous for cell therapy. Presently, there is no consensus for the mechanism of action. Many hypothesize that spheroid formation potentiates cell function by generating a hypoxic core within spheroids of sufficiently large diameters. The purpose of this study was to experimentally determine whether a hypoxic core is generated in MSC spheroids by measuring oxygen tension in aggregates of increasing diameter and correlatin
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Bell, Jordan, Shilpaa Mukundan, Matthew Teryek, Bo Lin, Biju Parekkadan, and Leo Chan. "Abstract 184: High-throughput chemotherapeutic drug screening of tumor spheroids with individual spheroid results using image cytometry." Cancer Research 82, no. 12_Supplement (2022): 184. http://dx.doi.org/10.1158/1538-7445.am2022-184.

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Abstract Three-dimensional cancer models have gained popularity for in vitro studies of chemotherapeutic compounds by providing a more physiologically relevant analog of gas, nutrient, and drug diffusion throughout the tumor microenvironment. Some 3D assays are performed to study individual spheroids over time, where a majority of these assays rely on maintaining a single spheroid in each well of a 96-well round-bottom ultra-low attachment plate, limiting the number of spheroids in a study. Other assays may gather population-level data from large ensembles of spheroids grown together, but the
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13

Lewis, Natasha S., Emily EL Lewis, Margaret Mullin, Helen Wheadon, Matthew J. Dalby, and Catherine C. Berry. "Magnetically levitated mesenchymal stem cell spheroids cultured with a collagen gel maintain phenotype and quiescence." Journal of Tissue Engineering 8 (January 1, 2017): 204173141770442. http://dx.doi.org/10.1177/2041731417704428.

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Multicellular spheroids are an established system for three-dimensional cell culture. Spheroids are typically generated using hanging drop or non-adherent culture; however, an emerging technique is to use magnetic levitation. Herein, mesenchymal stem cell spheroids were generated using magnetic nanoparticles and subsequently cultured within a type I collagen gel, with a view towards developing a bone marrow niche environment. Cells were loaded with magnetic nanoparticles, and suspended beneath an external magnet, inducing self-assembly of multicellular spheroids. Cells in spheroids were viable
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Jang, JunHwee, and Eun-Jung Lee. "Rapid Formation of Stem Cell Spheroids Using Two-Dimensional MXene Particles." Processes 9, no. 6 (2021): 957. http://dx.doi.org/10.3390/pr9060957.

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Cell spheroids have been studied as a biomimic medicine for tissue healing using cell sources. Rapid cell spheroid production increases cell survival and activity as well as the efficiency of mass production by reducing processing time. In this study, two-dimensional MXene (Ti3C2) particles were used to form mesenchymal stem cell spheroids, and the optimal MXene concentration, spheroid-production times, and bioactivity levels of spheroid cells during this process were assessed. A MXene concentration range of 1 to 10 μg/mL induced spheroid formation within 6 h. The MXene-induced spheroids exhib
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Das, Viswanath, Tomáš Fürst, Soňa Gurská, Petr Džubák, and Marián Hajdúch. "Reproducibility of Uniform Spheroid Formation in 384-Well Plates." Journal of Biomolecular Screening 21, no. 9 (2016): 923–30. http://dx.doi.org/10.1177/1087057116651867.

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Spheroid cultures of cancer cells reproduce the spatial dimension–induced in vivo tumor traits more effectively than the conventional two-dimensional cell cultures. With growing interest in spheroids for high-throughput screening (HTS) assays, there is an increasing demand for cost-effective miniaturization of reproducible spheroids in microtiter plates (MPs). However, well-to-well variability in spheroid size, shape, and growth is a frequently encountered problem with almost every culture method that has prevented the transfer of spheroids to the HTS platform. This variability partly arises d
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Prabhakaran, Vinothini, Anya Sobrattee, Ferry P. W. Melchels, and Jennifer Z. Paxton. "ADVANCING THE FABRICATION OF 3D MINI-TISSUE ENTHESIS CONSTRUCTS: CHARACTERIZATION OF BONE, TENDON, AND BMSC SPHEROIDS." Orthopaedic Proceedings 105-B, SUPP_16 (2023): 42. http://dx.doi.org/10.1302/1358-992x.2023.16.042.

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AbstractObjectivesThe enthesis is a specialised structure at the interface between bone and tendon with gradual integration to maintain functionality and integrity. In the process of fabricating an in-vitro model of this complex structure, this study aims to investigate growth and maturation of bone, tendon and BMSC spheroids followed by 3D mini-tissue production.MethodsCell spheroids Spheroids of differentiated rat osteoblasts (dRObs), rat tendon fibroblasts (RTFs) and bone marrow stem cells (BMSC) were generated by culturing in 96 well U bottom cell repellent plates. With dROb spheroids prev
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17

Liao, Fang-Chun, Yang-Kao Wang, Ming-Yang Cheng, and Ting-Yuan Tu. "A Preliminary Investigation of Embedding In Vitro HepaRG Spheroids into Recombinant Human Collagen Type I for the Promotion of Liver Differentiation." Polymers 14, no. 9 (2022): 1923. http://dx.doi.org/10.3390/polym14091923.

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Background: In vitro three-dimensional (3D) hepatic spheroid culture has shown great promise in toxicity testing because it better mimics the cell–cell and cell–matrix interactions found in in vivo conditions than that of the traditional two-dimensional (2D) culture. Despite embedding HepaRG spheroids with collagen type I (collagen I) extracellular matrix (ECM) revealed a much better differentiation capability, almost all the collagen utilized in in vitro hepatocytes cultures is animal-derived collagen that may limit its use in human toxicity testing. Method: Here, a preliminary investigation
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18

Shimoto, Takeshi, Xiu-Ying Zhang, Shizuka Akieda, Atsushi Ishikawa, Hidehiko Higaki, and Koichi Nakayama. "Analysis of Cell Spheroid Morphological Characteristics Using the Spheroid Morphology Evaluation System." Journal of Robotics and Mechatronics 30, no. 5 (2018): 819–26. http://dx.doi.org/10.20965/jrm.2018.p0819.

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Our research group established a technology for forming three-dimensional cell constructs to regenerate osteochondro cells without scaffolding. The established technology employed spheroids to form cell constructs. We also developed a method for arranging spheroids in arbitrary positions to form cell constructs in complex shapes. However, we could only form cell constructs as expected when the formed spheroids were the appropriate sizes. This study, therefore, aimed to chronologically analyze the spheroid morphological characteristics of rabbit mechanical stem cells using the developed spheroi
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Tenschert, Esther, Johann Kern, Annette Affolter, Nicole Rotter, and Anne Lammert. "Optimisation of Conditions for the Formation of Spheroids of Head and Neck Squamous Cell Carcinoma Cell Lines for Use as Animal Alternatives." Alternatives to Laboratory Animals 50, no. 6 (2022): 414–22. http://dx.doi.org/10.1177/02611929221135042.

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The use of in vitro 3-D cell culture models in cancer research has yielded substantial gains in knowledge on various aspects of tumour biology. Such cell culture models could be useful in the study of head and neck squamous cell carcinoma (HNSCC), where mimicking intratumoral and intertumoral heterogeneity is especially challenging. Our research aims to establish 3-D spheroid models for HNSCC that reproduce in vitro the connections between tumour cells and the surrounding microenvironment. The aims of this study were to determine the optimal conditions for the culture and use of spheroids from
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Stöhr, Daniela, Jens O. Schmid, Tobias B. Beigl, et al. "Stress-induced TRAILR2 expression overcomes TRAIL resistance in cancer cell spheroids." Cell Death & Differentiation 27, no. 11 (2020): 3037–52. http://dx.doi.org/10.1038/s41418-020-0559-3.

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Abstract The influence of 3D microenvironments on apoptosis susceptibility remains poorly understood. Here, we studied the susceptibility of cancer cell spheroids, grown to the size of micrometastases, to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Interestingly, pronounced, spatially coordinated response heterogeneities manifest within spheroidal microenvironments: In spheroids grown from genetically identical cells, TRAIL-resistant subpopulations enclose, and protect TRAIL-hypersensitive cells, thereby increasing overall treatment resistance. TRAIL-resistant layers form
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O'Rourke, John P., Mathew Saunders, and Valerie Sanchez. "Abstract 186: Advances in 3D cell culture analysis: Utilizing novel flow cytometry technology for rapid analysis of intact spheroids." Cancer Research 82, no. 12_Supplement (2022): 186. http://dx.doi.org/10.1158/1538-7445.am2022-186.

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Abstract Cancer cells grown in two dimensional (2D) monolayers are a convenient model to use for basic research and in generating lead candidates in the drug discovery process. However, cells grown in 2D cultures lack many of the structural, biological, and functional attributes of solid tumors, which contributes to the high clinical failure rates for biologic and small molecule drugs. Multicellular three-dimensional (3D) tumor spheroids are advanced models which more faithfully mimic the physiological tumor milieu and is more predictive of therapeutic efficacy than traditional monolayer cultu
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Molika, Piyatida, Kittinun Leetanaporn, Wararat Chiangjong, Pongsakorn Choochuen, and Raphatphorn Navakanitworakul. "Proteomic Analysis Reveals Cadherin, Actin, and Focal Adhesion Molecule-Mediated Formation of Cervical Cancer Spheroids." Cells 13, no. 23 (2024): 2004. https://doi.org/10.3390/cells13232004.

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Cancer spheroids are spherical, three-dimensional (3D), in vitro assemblies of cancer cells, which are gaining importance as a useful model in cancer behavior studies. Designed to simulate key features of the in vivo tumor microenvironment, spheroids offer reliable insights for drug screening and testing applications. We observed contrasting phenotypes in 3D cervical cancer (CC) cultures. Thus, in this study, we compared the proteomes of 3D and traditional two-dimensional (2D) cultures of CC cell lines, HeLa, SiHa, and C33A. When cultured in in-house poly-(2-hydroxyethyl methacrylate)-coated p
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Ikeda-Motonakano, Reiko, Fumika Hirabayashi-Nishimuta, Naomi Yada, et al. "Fabrication of a Three-Dimensional Spheroid Culture System for Oral Squamous Cell Carcinomas Using a Microfabricated Device." Cancers 15, no. 21 (2023): 5162. http://dx.doi.org/10.3390/cancers15215162.

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Cancer stem cells (CSCs) are considered to be responsible for recurrence, metastasis, and resistance to treatment in many types of cancers; therefore, new treatment strategies targeting CSCs are attracting attention. In this study, we fabricated a polyethylene glycol-tagged microwell device that enabled spheroid formation from human oral squamous carcinoma cells. HSC-3 and Ca9-22 cells cultured in the microwell device aggregated and generated a single spheroid per well within 24–48 h. The circular shape and smooth surface of spheroids were maintained for up to five days, and most cells compris
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Dabade, Vivekanand, Navaneeth K. Marath, and Ganesh Subramanian. "The effect of inertia on the orientation dynamics of anisotropic particles in simple shear flow." Journal of Fluid Mechanics 791 (February 24, 2016): 631–703. http://dx.doi.org/10.1017/jfm.2016.14.

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It is well known that, under inertialess conditions, the orientation vector of a torque-free neutrally buoyant spheroid in an ambient simple shear flow rotates along so-called Jeffery orbits, a one-parameter family of closed orbits on the unit sphere centred around the direction of the ambient vorticity (Jeffery, Proc. R. Soc. Lond. A, vol. 102, 1922, pp. 161–179). We characterize analytically the irreversible drift in the orientation of such torque-free spheroidal particles of an arbitrary aspect ratio, across Jeffery orbits, that arises due to weak inertial effects. The analysis is valid in
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Park, Yea-In, Rackhyun Park, Siyun Lee, et al. "AMPK Knockout Impairs the Formation of Three-Dimensional Spheroids." Life 15, no. 4 (2025): 525. https://doi.org/10.3390/life15040525.

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AMP-activated protein kinase (AMPK) is an important regulator of cellular energy homeostasis, and AMPK contributes to cell growth, apoptosis, and autophagy. Although most cell studies have been performed using two-dimensional (2D) cell culture, recent studies have demonstrated that the three-dimensional (3D) spheroid technique is helpful in various cell research fields, such as tumor biology, due to its resemblance to the 3D tissue structure. However, the role of AMPK in 3D spheroid formation has not been characterized clearly. This study used the AMPK knockout cell line to examine the role of
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26

Madhavan, Mathangi, Devina Jaiswal, Sarah Karlberg, et al. "Electron microscopy imaging and mechanical characterization of T47D multicellular tumor spheroids–Older spheroids reduce interstitial space and become stiffer." PLOS ONE 18, no. 5 (2023): e0286291. http://dx.doi.org/10.1371/journal.pone.0286291.

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Multicellular cancer spheroids are an in vitro tissue model that mimics the three-dimensional microenvironment. As spheroids grow, they develop the gradients of oxygen, nutrients, and catabolites, affecting crucial tumor characteristics such as proliferation and treatment responses. The measurement of spheroid stiffness provides a quantitative measure to evaluate such structural changes over time. In this report, we measured the stiffness of size-matched day 5 and day 20 tumor spheroids using a custom-built microscale force sensor and conducted transmission electron microscopy (TEM) imaging to
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Azizipour, Neda, Rahi Avazpour, Mohamad Sawan, Abdellah Ajji, and Derek H. Rosenzweig. "Surface Optimization and Design Adaptation toward Spheroid Formation On-Chip." Sensors 22, no. 9 (2022): 3191. http://dx.doi.org/10.3390/s22093191.

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Spheroids have become an essential tool in preclinical cancer research. The uniformity of spheroids is a critical parameter in drug test results. Spheroids form by self-assembly of cells. Hence, the control of homogeneity of spheroids in terms of size, shape, and density is challenging. We developed surface-optimized polydimethylsiloxane (PDMS) biochip platforms for uniform spheroid formation on-chip. These biochips were surface modified with 10% bovine serum albumin (BSA) to effectively suppress cell adhesion on the PDMS surface. These surface-optimized platforms facilitate cell self-aggregat
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Chen, Kai, Xianqi Li, Ni Li, et al. "Spontaneously Formed Spheroids from Mouse Compact Bone-Derived Cells Retain Highly Potent Stem Cells with Enhanced Differentiation Capability." Stem Cells International 2019 (May 5, 2019): 1–13. http://dx.doi.org/10.1155/2019/8469012.

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The results from our recent study showed the presence of two distinct spheroid-forming mechanisms, i.e., spontaneous and mechanical. In this study, we focused on the spontaneously formed spheroids, and the character of spontaneously formed spheroids from mouse compact bone-derived cells (CBDCs) was explored. Cells from (C57BL/6J) mouse leg bones were isolated, and compact bone-derived cells were cultured after enzymatic digestion. Spontaneous spheroid formation was achieved on a culture plate with specific water contact angle as reported. The expression levels of embryonic stem cell markers we
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Vella, Nathan, Diogo Estêvão, Tânia Cruz, Maria José Oliveira, Anthony George Fenech, and Vanessa Petroni Magri. "Abstract LB176: Targeting the PI3K/Akt/mTOR pathway in non-small cell lung cancer spheroids." Cancer Research 84, no. 7_Supplement (2024): LB176. http://dx.doi.org/10.1158/1538-7445.am2024-lb176.

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Abstract A major barrier in lung cancer pre-clinical research is the lack of simple, replicative and reproducible cell culture models. Most studies are still focused on 2D, completely ignoring cell-to-cell interactions, in vivo tissue architecture and the surrounding microenvironment. To address this void in cancer research, we aimed to develop a biomimetic 3D lung cancer spheroid model that can be used as a more reliable tool for pharmacological studies. Therefore, 3D spheroids of A549 (adenocarcinoma), H460 (large cell carcinoma) and H520 (squamous cell carcinoma) non-small cell lung cancer
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Mattapally, Saidulu, Wuqiang Zhu, Vladimir G. Fast, et al. "Spheroids of cardiomyocytes derived from human-induced pluripotent stem cells improve recovery from myocardial injury in mice." American Journal of Physiology-Heart and Circulatory Physiology 315, no. 2 (2018): H327—H339. http://dx.doi.org/10.1152/ajpheart.00688.2017.

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The microenvironment of native heart tissue may be better replicated when cardiomyocytes are cultured in three-dimensional clusters (i.e., spheroids) than in monolayers or as individual cells. Thus, we differentiated human cardiac lineage-induced pluripotent stem cells in cardiomyocytes (hiPSC-CMs) and allowed them to form spheroids and spheroid fusions that were characterized in vitro and evaluated in mice after experimentally induced myocardial infarction (MI). Synchronized contractions were observed within 24 h of spheroid formation, and optical mapping experiments confirmed the presence of
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Särchen, Vinzenz, Lisa Marie Reindl, Sara Wiedemann, et al. "Characterization of BV6-Induced Sensitization to the NK Cell Killing of Pediatric Rhabdomyosarcoma Spheroids." Cells 12, no. 6 (2023): 906. http://dx.doi.org/10.3390/cells12060906.

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Although the overall survival in pediatric rhabdomyosarcoma (RMS) has increased over the last decades, the most aggressive subtype of alveolar RMS is in dire need of novel treatment strategies. RMS cells evade cell death induction and immune control by increasing the expression of inhibitors of apoptosis proteins (IAPs), which can be exploited and targeted with stimulation with Smac mimetics. Here, we used the Smac mimetic BV6 to re-sensitize RMS spheroids to cell death, which increased killing induced by natural killer (NK) cells. Single BV6 treatment of RMS spheroids did not reduce spheroida
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Fritz, Jamie Lee, Olga Collins, Parima Saxena, et al. "A Novel Role for NUAK1 in Promoting Ovarian Cancer Metastasis through Regulation of Fibronectin Production in Spheroids." Cancers 12, no. 5 (2020): 1250. http://dx.doi.org/10.3390/cancers12051250.

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Epithelial ovarian cancer (EOC) has a unique mode of metastasis, where cells shed from the primary tumour, form aggregates called spheroids to evade anoikis, spread through the peritoneal cavity, and adhere to secondary sites. We previously showed that the master kinase Liver kinase B1 (LKB1) is required for EOC spheroid viability and metastasis. We have identified novel (nua) kinase 1 (NUAK1) as a top candidate LKB1 substrate in EOC cells and spheroids using a multiplex inhibitor beads-mass spectrometry approach. We confirmed that LKB1 maintains NUAK1 phosphorylation and promotes its stabiliz
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Boylan, Kristin L. M., Rory D. Manion, Heena Shah, Keith M. Skubitz, and Amy P. N. Skubitz. "Inhibition of Ovarian Cancer Cell Spheroid Formation by Synthetic Peptides Derived from Nectin-4." International Journal of Molecular Sciences 21, no. 13 (2020): 4637. http://dx.doi.org/10.3390/ijms21134637.

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The formation of 3D multicellular spheroids in the ascites fluid of ovarian cancer patients is an understudied component of the disease progression. Spheroids are less sensitive to chemotherapy, in part due to the protection afforded by their structure, but also due to their slower proliferation rate. Previous studies suggest that the cell adhesion molecule Nectin-4 plays a key role in the formation of ovarian cancer spheroids. In this study, we further examined the role of Nectin-4 at early time points in spheroid formation using real-time digital photography. Human NIH:OVCAR5 ovarian cancer
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Chen, Li-Chi, Hsin-Wen Wang, and Chieh-Cheng Huang. "Modulation of Inherent Niches in 3D Multicellular MSC Spheroids Reconfigures Metabolism and Enhances Therapeutic Potential." Cells 10, no. 10 (2021): 2747. http://dx.doi.org/10.3390/cells10102747.

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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 afte
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Pan, Rong, Xiaoyan Yang, Ke Ning, Yuanyuan Xie, Feng Chen, and Ling Yu. "Recapitulating the Drifting and Fusion of Two-Generation Spheroids on Concave Agarose Microwells." International Journal of Molecular Sciences 24, no. 15 (2023): 11967. http://dx.doi.org/10.3390/ijms241511967.

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Cells with various structures and proteins naturally come together to cooperate in vivo. This study used cell spheroids cultured in agarose micro-wells as a 3D model to study the movement of cells or spheroids toward other spheroids. The formation dynamics of tumor spheroids and the interactions of two batches of cells in the agarose micro-wells were studied. The results showed that a concave bottom micro-well (diameter: 2 mm, depth: 2 mm) prepared from 3% agarose could be used to study the interaction of two batches of cells. The initial tumor cell numbers from 5 × 103 cells/well to 6 × 104 c
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Grayson, Korie A., Nidhi Jyotsana, Nerymar Ortiz-Otero, and Michael R. King. "Overcoming TRAIL-resistance by sensitizing prostate cancer 3D spheroids with taxanes." PLOS ONE 16, no. 3 (2021): e0246733. http://dx.doi.org/10.1371/journal.pone.0246733.

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Three-dimensional spheroid cultures have been shown to better physiologically mimic the cell-cell and cell-matrix interactions that occur in solid tumors more than traditional 2D cell cultures. One challenge in spheroid production is forming and maintaining spheroids of uniform size. Here, we developed uniform, high-throughput, multicellular spheroids that self-assemble using microwell plates. DU145 and PC3 cells were cultured as 2D monolayers and 3D spheroids to compare sensitization of TRAIL-resistance cancer cells to TRAIL mediated apoptosis via chemotherapy based on dimensionality. Monocul
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Sakai, Yasuyuki, Katsutoshi Naruse, Ikuo Nagashima, Tetsuichiro Muto, and Motoyuki Suzuki. "Short-Term Hypothermic Preservation of Porcine Hepatocyte Spheroids using uw Solution." Cell Transplantation 5, no. 4 (1996): 505–11. http://dx.doi.org/10.1177/096368979600500410.

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The feasibility of University of Wisconsin (UW) solution in short-term hypothermic preservation of porcine hepatocyte spheroids was investigated, because they have great potential in bioartificial liver (BAL) systems. Porcine hepatocyte spheroids preserved for 3 days expressed almost comparable levels of albumin secretion as those without preservation, during 8 subsequent days of recultivation in continuous rotational culture, whereas isolated single cells did not reorganize into spheroids and completely lost their function in recultivation. Although for 3-day–preserved spheroids, the albumin
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Roy, Marie, Corentin Alix, Ayache Bouakaz, Sophie Serrière, and Jean-Michel Escoffre. "Tumor Spheroids as Model to Design Acoustically Mediated Drug Therapies: A Review." Pharmaceutics 15, no. 3 (2023): 806. http://dx.doi.org/10.3390/pharmaceutics15030806.

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Tumor spheroids as well as multicellular tumor spheroids (MCTSs) are promising 3D in vitro tumor models for drug screening, drug design, drug targeting, drug toxicity, and validation of drug delivery methods. These models partly reflect the tridimensional architecture of tumors, their heterogeneity and their microenvironment, which can alter the intratumoral biodistribution, pharmacokinetics, and pharmacodynamics of drugs. The present review first focuses on current spheroid formation methods and then on in vitro investigations exploiting spheroids and MCTS for designing and validating acousti
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Goisnard, Antoine, Clémence Dubois, Pierre Daumar, et al. "The New Serum-Free OptiPASS® Medium in Cold and Oxygen-Free Conditions: An Innovative Conservation Method for the Preservation of MDA-MB-231 Triple Negative Breast Cancer Spheroids." Cancers 13, no. 8 (2021): 1945. http://dx.doi.org/10.3390/cancers13081945.

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Cancer spheroids are very effective preclinical models to improve anticancer drug screening. In order to optimize and extend the use of spheroid models, these works were focused on the development of a new storage concept to maintain these models in the longer term using the Triple-Negative Breast Cancer MDA-MB-231 spheroid models. The results highlight that the combination of a temperature of 4 °C and oxygen-free conditions allowed the spheroid characteristics of OptiPASS® serum-free culture medium to preserve the spheroid characteristics during 3-, 5- or 7-day-long storage. Indeed, after sto
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Roh, Hyewon, Hwisoo Kim, and Je-Kyun Park. "Construction of a Fibroblast-Associated Tumor Spheroid Model Based on a Collagen Drop Array Chip." Biosensors 11, no. 12 (2021): 506. http://dx.doi.org/10.3390/bios11120506.

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Spheroid, a 3D aggregate of tumor cells in a spherical shape, has overcome the limitations of conventional 3D cell models to accurately mimic the in-vivo environment of a human body. The spheroids are cultured with other primary cells and embedded in collagen drops using hang drop plates and low-attachment well plates to construct a spheroid–hydrogel model that better mimics the cell–cell and cell–extracellular matrix (ECM) interactions. However, the conventional methods of culturing and embedding spheroids into ECM have several shortcomings. The procedure of transferring a single spheroid at
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Fröhlich, Eleonore. "Issues with Cancer Spheroid Models in Therapeutic Drug Screening." Current Pharmaceutical Design 26, no. 18 (2020): 2137–48. http://dx.doi.org/10.2174/1381612826666200218094200.

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In vitro screening for anti-cancer agents currently uses mainly cell lines in 2D culture. It is generally assumed that 3D culture, namely spheroids, represents physiologically more relevant models for tumors. Unfortunately, drug testing in spheroids is not as easy and reproducible as in 2D culture because there are factors that limit the universal use of spheroids as screening platforms. Technical problems in the generation of uniform spheroids, cell/tumor-specific differences in the ability to form spheroids, and more complex readout parameters are the main reasons for differences between sph
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Zhuang, Pei, Yi-Hua Chiang, Maria Serafim Fernanda, and Mei He. "Using Spheroids as Building Blocks Towards 3D Bioprinting of Tumor Microenvironment." International Journal of Bioprinting 7, no. 4 (2021): 444. http://dx.doi.org/10.18063/ijb.v7i4.444.

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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
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Wendel, Jillian R. H., Xiyin Wang, Lester J. Smith, and Shannon M. Hawkins. "Three-Dimensional Biofabrication Models of Endometriosis and the Endometriotic Microenvironment." Biomedicines 8, no. 11 (2020): 525. http://dx.doi.org/10.3390/biomedicines8110525.

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Endometriosis occurs when endometrial-like tissue grows outside the uterine cavity, leading to pelvic pain, infertility, and increased risk of ovarian cancer. The present study describes the optimization and characterization of cellular spheroids as building blocks for Kenzan scaffold-free method biofabrication and proof-of-concept models of endometriosis and the endometriotic microenvironment. The spheroid building blocks must be of a specific diameter (~500 μm), compact, round, and smooth to withstand Kenzan biofabrication. Under optimized spheroid conditions for biofabrication, the endometr
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Shahi Thakuri, Pradip, and Hossein Tavana. "Single and Combination Drug Screening with Aqueous Biphasic Tumor Spheroids." SLAS DISCOVERY: Advancing the Science of Drug Discovery 22, no. 5 (2017): 507–15. http://dx.doi.org/10.1177/2472555217698817.

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Spheroids of cancer cells represent a physiologic model of solid tumors for cancer drug screening. Despite this known benefit, difficulties with generating large quantities of uniformly sized spheroids in standard plates, individually addressing spheroids with drug compounds, and quantitatively analyzing responses of cancer cells have hindered the use of spheroids in high-throughput screening applications. Recently, we addressed this challenge by using an aqueous two-phase system technology to generate a spheroid within an aqueous drop immersed in a second, immiscible aqueous phase. Integratin
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Fok, Sheridan, Yoanna Ivanova, Victoria Kriuchkovskaia, and Brendan Harley. "Abstract 238: Investigating size-dependent invasion behaviors and therapeutic responses of the 42MGBA glioblastoma spheroids." Cancer Research 84, no. 6_Supplement (2024): 238. http://dx.doi.org/10.1158/1538-7445.am2024-238.

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Abstract Introduction: Glioblastoma (GBM) is one of the most aggressive malignant brain tumors. Many studies have reported that the tumor microenvironment (TME) contributes greatly to invasion and drug resistance of GBM. Our lab has previously described a tri-culture model using methacrylamide-functionalized gelatin (GelMA) with brain microvascular endothelial cells (BMVEC), human normal astrocytes (NHA), and human brain vascular pericyte (HBVP) recapitulated the in vivo brain microenvironment. However, phenotypic drug response was only observed under supraphysiological dosage. To evaluate the
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Conz, Marco, Francesca Scognamiglio, Ivan Donati, et al. "Early Chondrogenic Differentiation of Spheroids for Cartilage Regeneration: Investigation of the Structural and Biological Role of a Lactose-Modified Chitosan." Polysaccharides 6, no. 2 (2025): 47. https://doi.org/10.3390/polysaccharides6020047.

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Long-term solutions for cartilage repair after injury are currently being investigated, with most research aiming to exploit the regenerative and chondrogenic differentiation potential of stem-cell-based spheroids. The incorporation of the bioactive polymer CTL, a lactose-modified chitosan, into spheroids is a strategy to improve cell viability and accelerate type II collagen gene expression. In this work, the role of CTL in influencing the dynamics of spheroid formation and its interplay with cell membrane adhesion molecules (integrins and cadherins) and cytoskeletal components is elucidated.
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St-Georges-Robillard, Amélie, Maxime Cahuzac, Benjamin Péant, et al. "Long-term fluorescence hyperspectral imaging of on-chip treated co-culture tumour spheroids to follow clonal evolution." Integrative Biology 11, no. 4 (2019): 130–41. http://dx.doi.org/10.1093/intbio/zyz012.

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Abstract Multicellular tumour spheroids are an ideal in vitro tumour model to study clonal heterogeneity and drug resistance in cancer research because different cell types can be mixed at will. However, measuring the individual response of each cell population over time is challenging: current methods are either destructive, such as flow cytometry, or cannot image throughout a spheroid, such as confocal microscopy. Our group previously developed a wide-field fluorescence hyperspectral imaging system to study spheroids formed and cultured in microfluidic chips. In the present study, two subclo
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Puscz, Flemming, Noah Jozsef Hatem, Sonja Verena Schmidt, et al. "Implementation of a CAM Assay Using Fibrosarcoma Spheroids." International Journal of Molecular Sciences 26, no. 11 (2025): 5318. https://doi.org/10.3390/ijms26115318.

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Fibrosarcomas represent a rare but highly aggressive tumor entity among soft tissue tumors. Due to its rarity, questions regarding its development and pathophysiology remain unclear. The chorioallantoic membrane (CAM) assay represents an easily available method to investigate tumors on a growth membrane, live and in ovo. The following study was established to test whether the growth of fibrosarcoma spheroids on the CAM was possible and to critically review their applicability for downstream investigations. The shells of fertilized chicken eggs were opened and the previously prepared HT1080 cel
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Royo, Felix, Clara Garcia-Vallicrosa, Maria Azparren-Angulo, Guillermo Bordanaba-Florit, Silvia Lopez-Sarrio, and Juan Manuel Falcon-Perez. "Three-Dimensional Hepatocyte Spheroids: Model for Assessing Chemotherapy in Hepatocellular Carcinoma." Biomedicines 12, no. 6 (2024): 1200. http://dx.doi.org/10.3390/biomedicines12061200.

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BACKGROUND: Three-dimensional cellular models provide a more comprehensive representation of in vivo cell properties, encompassing physiological characteristics and drug susceptibility. METHODS: Primary hepatocytes were seeded in ultra-low attachment plates to form spheroids, with or without tumoral cells. Spheroid structure, cell proliferation, and apoptosis were analyzed using histological staining techniques. In addition, extracellular vesicles were isolated from conditioned media by differential ultracentrifugation. Spheroids were exposed to cytotoxic drugs, and both spheroid growth and ce
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Mao, Wenbin, and Alexander Alexeev. "Motion of spheroid particles in shear flow with inertia." Journal of Fluid Mechanics 749 (May 14, 2014): 145–66. http://dx.doi.org/10.1017/jfm.2014.224.

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AbstractIn this article, we investigate the motion of a solid spheroid particle in a simple shear flow. Using a lattice Boltzmann method, we examine individual effects of fluid inertia and particle rotary inertia as well as their combination on the dynamics and trajectory of spheroid particles at low and moderate Reynolds numbers. The motion of a single spheroid is shown to be dependent on the particle Reynolds number, particle aspect ratio, particle initial orientation and the Stokes number. Spheroids with random initial orientations are found to drift to stable orbits influenced by fluid ine
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