Advances in multicellular spheroids formation

Cui, Xiaolin; Hartanto, Yusak; Zhang, Hu

doi:10.1098/rsif.2016.0877

Cited by 409 publications

(387 citation statements)

References 131 publications

(172 reference statements)

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“…These methods promote the formation of 3D microtissues as cellular aggregates known as spheroids or multicellular tumor spheroids, in which cells produce their own ECM (Knight & Przyborski, 2015). In the agitation-based techniques, such as those based on the utilization of spinner flasks, gyratory shakers, roller tubes, or rotating wall vessels (e.g., NASA bioreactor), cells spontaneously aggregate into spheroids by keeping them in continuous stirring conditions that avoid the cells adhesion to the surfaces (Cui, Hartanto, & Zhang, 2017). In the agitation-based techniques, such as those based on the utilization of spinner flasks, gyratory shakers, roller tubes, or rotating wall vessels (e.g., NASA bioreactor), cells spontaneously aggregate into spheroids by keeping them in continuous stirring conditions that avoid the cells adhesion to the surfaces (Cui, Hartanto, & Zhang, 2017).…”

Section: Scaffold-free 3d Cell Culturesmentioning

confidence: 99%

“…Benien and Swami (2014), Cui et al (2017) Hanging drop technique (HDT) Simple; low cost; no specialized equipment required; spheroids size and shape is reproducible; spheroids can be produced in individual compartments. Laborious; not stable; impractical long-term culture; hard to scale up (without the use of commercial products); hard to perform drugs screening (without the use of commercial products); not-compatible with HTS (without the use of commercial products).…”

Section: Spinner Flasksmentioning

confidence: 99%

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3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs

Nunes

Barros

Costa

et al. 2018

Biotech & Bioengineering

541

445

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Three-dimensional cell culture models, such as spheroids, can be used in the process of the development of new anticancer agents because they are able to closely mimic the main features of human solid tumors, namely their structural organization, cellular layered assembling, hypoxia, and nutrient gradients. These properties imprint to the spheroids an anticancer therapeutics resistance profile, which is similar to that displayed by human solid tumors. In this review, an overview of the drug resistance mechanisms observed in 3D tumor spheroids is provided. Furthermore, comparisons between the therapeutics resistance profile exhibited by spheroids, and 2D cell cultures are presented. Finally, examples of the therapeutic approaches that have been developed to surpass the drug resistance mechanisms exhibited by spheroids are described. HIGHLIGHTS•The suitability of 3D cell culture models for drug screening purposes is highlighted. •Spheroids and in vivo human solid tumors structural and functional similarities are emphasized.•The drug resistance mechanisms exhibited by spheroids are described.•Therapeutic approaches used to surpass spheroids' drug resistance mechanisms are described. K E Y W O R D Sdrug resistance, drugs, in vitro models, solid tumors, spheroids

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Section: Scaffold-free 3d Cell Culturesmentioning

confidence: 99%

Section: Spinner Flasksmentioning

confidence: 99%

3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs

Nunes

Barros

Costa

et al. 2018

Biotech & Bioengineering

541

445

View full text Add to dashboard Cite

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“…Oproti ná-dorovým buňkám majícím při kultivaci v monovrstvě na Petriho misce plochý "rozprostřený" tvar, vykazují buňky tvořící sféroid morfologii, která mnohem věrněji kopíruje morfologii buněk uvnitř nádoru, ze kterého byly odvozeny [47]. Dále buňky kultivované v monovrstvě proliferují v podstatě rovnoměrně, zatímco vytvořením buněčného sféroidu dochází ke vzniku rozdílných zón tvoře-ných buňkami v různých fázích buněč-MCS [43]. Na našem pracovišti se nejčastěji používá metoda visící kapkybuňky se nanesou v kapce na víčko kultivační nádoby a po jejím otočení vznikne kapka.…”

Section: D In Vitro Modelyunclassified

New Approaches for Chemosensitivity Testing in Malignant Diseases

Sommerová¹,

Michalová²,

Hrstka³

2018

Klin Onkol

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Východiska: Vzhledem k nezastupitelné úloze chemoterapie při léčbě nádorových onemocnění se onkologický výzkum zaměřil na zvýšení účinnosti jednotlivých léčiv a maximální zmírnění, ne-li kompletní potlačení nežádoucích účinků. Vhodná léčba je primárně volena podle základních klinicko-patologických dia gnostických kritérií, jako je velikost nádoru, stupeň diferenciace a přítom-nost či absence standardních markerů. Situaci však komplikuje variabilita mezi jednotlivými pacienty spolu se značnou heterogenitou vlastního nádoru. Detailní charakterizace intratumorální heterogenity a získání spolehlivějších ukazatelů účinnosti léčiv by tak mělo vést k posílení personalizované terapie. Vývoj a výběr spolehlivých modelů tudíž představuje důležitou otázku ve vý-zkumu zaměřeném na predikci citlivosti nádorových buněk k léčbě. Cíl: Práce shrnuje poznatky o testovacích systémech zaměřených na stanovení citlivosti či rezistence nádorových buněk k chemoterapii a jejich zavádění do onkologické praxe od prvních dnes již historických pokusů až po současnost se snahou posoudit jejich uplatnění ve stávající klinické praxi či blízké budoucnosti. Značný důraz je kladen na porovnání 2D a 3D in vitro buněčných modelů, neboť jejich význam a popularita konstantně narůstá. Pozornost je též věnovaná systémům in vivo, které v poslední době zaznamenaly nemalý progres a jsou v rámci klinických studií testovány k predikci odpovědi na podávanou terapii. Závěr: Práce uvádí stručný přehled testů chemosenzitivity a hodnotí význam jednotlivých testů vzhledem k jejich zapojení do rozhodovacího procesu a stratifikace pacientů s cílem predikovat klinickou odpověď konkrétních pacientů a přispět tak k rozvoji cílené personalizované terapie. Klíčová slovatechniky tkáňových kultur -individualizovaná medicína -screening léčiv -bio logické modely -nádorové buněčné linie -karcinom -cytotoxické testy SummaryBackground: Due to the irreplaceable role of chemotherapy in cancer treatment, research has focused on improving the efficacies of individual drugs and minimizing, or completely suppressing, their negative side effects. Based on long-term experience and the results of clinical trials, the selection of appropriate treatment is currently based on classical clinical dia gnostic criteria, such as tumor size, grade, and the presence or absence of standard markers. However, complications arise due to variability between patients and tumor heterogeneity. Characterization of intratumoral heterogeneity and acquisition of more reliable drug performance indicators should improve personalized therapy. Development and selection of suitable models are therefore important issues in cancer research focused on predicting sensitivity to therapy. Aim: This work provides an overview of various chemosensitivity tests that have been previously employed and those that are currently used. Great emphasis is placed on comparing 2D and 3D cell culture models, since their importance and popularity are increasing. Particular attention is paid to in vivo systems, which have significantl...

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“…The cell spheroids were then cultured in ultralow attachable culture dish (＃3262 Corning ® , Thermo Fisher Scientific) to minimize the cell attachment. The spheroid size and cell viability were measured daily for 7 days [36,45] .…”

Section: Methodsmentioning

confidence: 99%

Formation of cell spheroids using Standing Surface Acoustic Wave (SSAW)

Sriphutkiat¹,

Kasetsirikul²,

Zhou³

2024

IJB

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3D bioprinting becomes one of the popular approaches in the tissue engineering. In this emerging application, bioink is crucial for fabrication and functionality of constructed tissue. The use of cell spheroids as bioink can enhance the cell-cell interaction and subsequently the growth and differentiation of cells in the 3D printed construct with the minimum amount of other biomaterials. However, the conventional methods of preparing the cell spheroids have several limitations, such as long culture time, low-throughput, and medium modification. In this study, the formation of cell spheroids by SSAW was evaluated both numerically and experimentally in order to overcome the aforementioned limitations. The effects of excitation frequencies on the cell accumulation time, diameter of the formed cell spheroids, and subsequently, the growth and viability of cell spheroids in the culture medium over time were studied. Using the high-frequency (23.8 MHz) excitation, cell accumulation time to the pressure nodes could be reduced in comparison to that of the low-frequency (10.4 MHz) excitation, but in a smaller spheroid size. SSAW excitation at both frequencies does not affect the cell viability up to 7 days, > 90% with no statistical difference compared with the control group. In summary, SSAW can effectively prepare the cell spheroids as bioink for the future 3D bioprinting and various biotechnology applications (e.g., pharmaceutical drug screening and tissue engineering).

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Advances in multicellular spheroids formation

Cited by 409 publications

References 131 publications

3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs

3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs

New Approaches for Chemosensitivity Testing in Malignant Diseases

Formation of cell spheroids using Standing Surface Acoustic Wave (SSAW)

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