The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Advances in the formation, use and understanding of multi-cellular spheroids
Open accessAbstract
INTRODUCTION: Developing in vitro models for studying cell biology and cell physiology is of great importance to the fields of biotechnology, cancer research, drug discovery, toxicity testing, as well as the emerging fields of tissue engineering and regenerative medicine. Traditional two-dimensional (2D) methods of mammalian cell culture have several limitations and it is increasingly recognized that cells grown in a three-dimensional (3D) environment more closely represent normal cellular function due to the increased cell-to-cell interactions, and by mimicking the in vivo architecture of natural organs and tissues. AREAS COVERED: In this review, we discuss the methods to form 3D multi-cellular spheroids, the advantages and limitations of these methods, and assays used to characterize the function of spheroids. The use of spheroids has led to many advances in basic cell sciences, including understanding cancer cell interactions, creating models for drug discovery and cancer metastasis, and they are being investigated as basic units for engineering tissue constructs. As so, this review will focus on contributions made to each of these fields using spheroid models. EXPERT OPINION: Multi-cellular spheroids are rich in biological content and mimic better the in vivo environment than 2D cell culture. New technologies to form and analyze spheroids are rapidly increasing their adoption and expanding their applications.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Kalluri, R., & Zeisberg, M. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1877 · Cited by 4,538
The third dimension bridges the gap between cell culture and live tissue
Pampaloni, F., Reynaud, E. G., & Stelzer, E. H. K. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2236 · Cited by 2,817
Drug penetration in solid tumours
Minchinton, A. I., & Tannock, I. F. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1893 · Cited by 2,805
Cell and environment interactions in tumor microregions: the multicell spheroid model.
Sutherland, R. M. (1988) · Science · doi:10.1126/science.2451290 · Cited by 1,803
Simulation of biological cell sorting using a two-dimensional extended Potts model
Graner, F., & Glazier, J. A. (1992) · Physical Review Letters · doi:10.1103/physrevlett.69.2013 · Cited by 1,377
High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array
Tung, Y.-C., Hsiao, A. Y., Allen, S. G., Torisawa, Y.-S., Ho, M., & Takayama, S. (2011) · The Analyst · doi:10.1039/c0an00609b · Cited by 969
The differential adhesion hypothesis: a direct evaluation
Foty, R. A., & Steinberg, M. S. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2004.11.012 · Cited by 908 · cited 3×
“One such model, the differential adhesion hypothesis (DAH) posits that cell types self-segregate due to differences in cell-to-cell adhesion or apparent surface tension, with those cells of highest cohesion (like-to-like adhesion) sorting to the inside of a spheroid and those cells with lower cohesion sorting to the o…”
BackgroundMethodGene expression perturbation in vitro—A growing case for three-dimensional (3D) culture systems
Birgersdotter, A., Sandberg, R., & Ernberg, I. (2005) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2005.06.009 · Cited by 591
A Review of Three-Dimensional In Vitro Tissue Models for Drug Discovery and Transport Studies
Elliott, N. T., & Yuan, F. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22257 · Cited by 449
A novel 3D mammalian cell perfusion-culture system in microfluidic channels
Toh, Y.-C., Zhang, C., Zhang, J., Khong, Y. M., Chang, S., Samper, V. D., van Noort, D., Hutmacher, D. W., & Yu, H. (2007) · Lab on a Chip · doi:10.1039/b614872g · Cited by 414
Cited by
Advances in multicellular spheroids formation
Cui, X., Hartanto, Y., & Zhang, H. (2017) · Journal of The Royal Society Interface · doi:10.1098/rsif.2016.0877 · Cited by 508
Spheroid Culture of Mesenchymal Stem Cells
Cesarz, Z., & Tamama, K. (2016) · Stem Cells International · doi:10.1155/2016/9176357 · Cited by 475
3D cell culture systems modeling tumor growth determinants in cancer target discovery
Thoma, C. R., Zimmermann, M., Agarkova, I., Kelm, J. M., & Krek, W. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.03.001 · Cited by 478
Three-Dimensional Spheroids as In Vitro Preclinical Models for Cancer Research
Pinto, B., Henriques, A. C., Silva, P. M. A., & Bousbaa, H. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12121186 · Cited by 440
Life is 3D: Boosting Spheroid Function for Tissue Engineering
Laschke, M. W., & Menger, M. D. (2017) · Trends in Biotechnology · doi:10.1016/j.tibtech.2016.08.004 · Cited by 438
Metadata
- Authors
- Achilli, T.-M., Meyer, J., & Morgan, J. R.
- Venue
- Expert Opinion on Biological Therapy
- Publisher
- Informa UK Limited
- Published
- 2012-07-12
- Volume
- 12
- Issue
- 10
- Pages
- 1347-1360
- ISSN
- 1471-2598 (ISSN-L)
- 1744-7682
- OpenAlex
- W2154555172
- Cited by
- 572
- References
- 13
- FWCI
- 8.89
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Advances in the formation, use and understanding of multi-cellular spheroids. https://app.cochat.ai/papers/10.1517/14712598.2012.707181
- The paper
- Achilli, T.-M., Meyer, J., & Morgan, J. R. (2012). Advances in the formation, use and understanding of multi-cellular spheroids. Expert Opinion on Biological Therapy. https://doi.org/10.1517/14712598.2012.707181
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.