Multicellular Tumor Spheroids as an in Vivo–Like Tumor Model for Three-Dimensional Imaging of Chemotherapeutic and Nano Material Cellular Penetration

Ma, Huili; Jiang, Qiao; Han, Sang Mi; Wu, Yan; Tomshine, Jin C.; Wang, Dongliang; Gan, Yulin; Zou, Guozhang; Liang, Xing‐Jie

doi:10.2310/7290.2012.00012

Cited by 155 publications

(165 citation statements)

References 37 publications

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

“…[70] They verified that after 3 days of culture, the diameter of all spheroids increased overtime in a rate that was proportional to the initial number of cells seeded. In this way, spheroids produced with a higher initial cell number (1000 cells/well) were the first to attain sizes higher than 500 μm (approximately after 7 days of culture).…”

Section: Control the Spheroids Size By Using Fine-tuning The Initial mentioning

confidence: 96%

“…Spheroids size can be optimized by modulating the initial number of cells seeded on the non-adherent surfaces as observed by Ma et al [70] The authors seeded a different number of HeLa cells per well (62,125,250, 500, and 1000) to obtain spheroids by LOT in agarose (1% (w/v)) coated 96-well plates. [70] They verified that after 3 days of culture, the diameter of all spheroids increased overtime in a rate that was proportional to the initial number of cells seeded.…”

Section: Control the Spheroids Size By Using Fine-tuning The Initial mentioning

confidence: 99%

“…[42,60] Agar and agarose were the first biomaterials applied for the growth of spheroids by LOT. [15,37,38,[61][62][63][64][65][66][67][68][69][70] Nowadays, these two materials are extensively used due to their low cost and easy manipulation, which reduces the time spent in the plate-coating procedure ( Table 3). For the preparation of agar or agarose coated plates, first the biomaterials are fully dissolved in water or serum-free medium and then they are sterilized by autoclave.…”

Section: Biomaterials Used In the Plate-coating Proceduresmentioning

confidence: 99%

“…Cisplatin Breast cancer EMT-6 [24] Endometrial cancer Ishikawa [25] RL95-2 [25] KLE [25] Hypopharyngeal cancer FaDu [96] Ovarian cancer OVCAR8 [97] Oral cancer SCC25 [96] CAL27 [96] Chlorimipramine Glioma C6 [98] Cyclophosphamide Breast cancer EMT-6 [24] Diclofenac Liver tissue Hepatocytes obtained from patient [10] Hepatoma C3A [68] Docetaxel Cervical cancer HeLa [99] Colon cancer HT29 [99] Doxorubicin Cervical cancer HeLa [70] Endometrial cancer Ishikawa [25] RL95-2 [25] KLE [25] Hepatoma C3A [68] Huh7 [100] Lung cancer A549 [101] E-combretastatin A4 Melanoma C8161 [102] Breast cancer MDA 231 [102] (Continued) [26] PC3 [26] Fialuridine Liver tissue Hepatocytes obtained from patient [10] Fialuridine Hepatoma C3A [68] Gant61…”

Section: Cb13mentioning

confidence: 99%

See 3 more Smart Citations

Spheroids Formation on Non‐Adhesive Surfaces by Liquid Overlay Technique: Considerations and Practical Approaches

Costa

Melo‐Diogo

Moreira

et al. 2017

Biotechnology Journal

155

139

View full text Add to dashboard Cite

Scalable and reproducible production of 3D cellular spheroids is highly demanded, by pharmaceutical companies, for drug screening purposes during the pre-clinical evaluation phase. These 3D cellular constructs, unlike the monolayer culture of cells, can mimic different features of human tissues, including cellular organization, cell-cell and cell-extracellular matrix (ECM) interactions. Up to now, different techniques (scaffold-based and -free) have been used for spheroids formation, being the Liquid Overlay Technique (LOT) one of the most explored methodologies, due to its low cost and easy handling. Additionally, during the last few decades, this technique has been widely investigated in order to enhance its potential for being applied in high-throughput analysis. Herein, an overview of the LOT advances, practical approaches, and troubleshooting is provided for those researchers that intend to produce spheroids using LOT, for drug screening purposes. Moreover, the advantages of the LOT over the other scaffold-free techniques used for the spheroids formation are also addressed. Highlights • 2D cell culture drawbacks are summarized;• spheroids mimic the features of human tissues;• scaffold-based and scaffold-free technologies for spheroids production are discussed; • advantages of LOT over other scaffold-free techniques are highlighted; • LOT advances, practical approaches and troubleshooting are underlined.

show abstract

Section: Control the Spheroids Size By Using Fine-tuning The Initial mentioning

confidence: 96%

Section: Control the Spheroids Size By Using Fine-tuning The Initial mentioning

confidence: 99%

Section: Biomaterials Used In the Plate-coating Proceduresmentioning

confidence: 99%

Section: Cb13mentioning

confidence: 99%

See 2 more Smart Citations

Spheroids Formation on Non‐Adhesive Surfaces by Liquid Overlay Technique: Considerations and Practical Approaches

Costa

Melo‐Diogo

Moreira

et al. 2017

Biotechnology Journal

155

139

View full text Add to dashboard Cite

show abstract

“…18,19 However, despite these improved abilities of 2-P microscopy in comparison with standard (single photon) confocal microscopy, 20 it also faces some limitations. The scattering properties of 3-D cell cultures can still result in the non-uniform image intensity through a Z-stack, 21,22 and in the case of spherical 3-D cultures, can lead to the sections with darkened interiors due to the longer optical path through the centre of the spherical structures. Much of the scattering induced by 3-D tissues such as tumour spheroids occurs in the lipidaqueous interface, 23 and is due to the refractive index (RI) mismatch between the tissue and the imaging medium that results in blurred images and shallow imaging depth due to the loss of signal photons.…”

Section: Introductionmentioning

confidence: 99%

On-chip clearing of arrays of 3-D cell cultures and micro-tissues

et al. 2016

View full text Add to dashboard Cite

Three-dimensional (3-D) cell cultures are beneficial models for mimicking the complexities of in vivo tissues, especially in tumour studies where transport limitations can complicate response to cancer drugs. 3-D optical microscopy techniques are less involved than traditional embedding and sectioning, but are impeded by optical scattering properties of the tissues. Confocal and even two-photon microscopy limit sample imaging to approximately 100-200 lm depth, which is insufficient to image hypoxic spheroid cores. Optical clearing methods have permitted high-depth imaging of tissues without physical sectioning, but they are difficult to implement for smaller 3-D cultures due to sample loss in solution exchange. In this work, we demonstrate a microfluidic platform for high-throughput on-chip optical clearing of breast cancer spheroids using the SeeDB, Clear T2 , and ScaleSQ clearing methods. Although all three methods are able to effectively clear the spheroids, we find that SeeDB and ScaleSQ more effectively clear the sample than Clear T2 ; however, SeeDB induces green autofluorescence while ScaleS causes sample expansion. Our unique on-chip implementation permits clearing arrays of 3-D cultures using perfusion while monitoring the 3-D cultures throughout the process, enabling visualization of the clearing endpoint as well as monitoring of transient changes that could induce image artefacts. Our microfluidic device is compatible with on-chip 3-D cell culture, permitting the use of on-chip clearing at the endpoint after monitoring the same spheroids during their culture. This onchip method has the potential to improve readout from 3-D cultures, facilitating their use in cell-based assays for high-content drug screening and other applications. Published by AIP Publishing. [http://dx

show abstract

Alternative Models in Drug Discovery and Development Part I: In Silico and In Vitro Models

Romero

Vela

2014

In Vivo Models for Drug Discovery

View full text Add to dashboard Cite

Multicellular Tumor Spheroids as an in Vivo–Like Tumor Model for Three-Dimensional Imaging of Chemotherapeutic and Nano Material Cellular Penetration

Cited by 155 publications

References 37 publications

Spheroids Formation on Non‐Adhesive Surfaces by Liquid Overlay Technique: Considerations and Practical Approaches

Spheroids Formation on Non‐Adhesive Surfaces by Liquid Overlay Technique: Considerations and Practical Approaches

On-chip clearing of arrays of 3-D cell cultures and micro-tissues

Alternative Models in Drug Discovery and Development Part I: In Silico and In Vitro Models

Contact Info

Product

Resources

About