Recent advances in three‐dimensional multicellular spheroid culture for biomedical research
Abstract
Many types of mammalian cells can aggregate and differentiate into 3-D multicellular spheroids when cultured in suspension or a nonadhesive environment. Compared to conventional monolayer cultures, multicellular spheroids resemble real tissues better in terms of structural and functional properties. Multicellular spheroids formed by transformed cells are widely used as avascular tumor models for metastasis and invasion research and for therapeutic screening. Many primary or progenitor cells on the other hand, show significantly enhanced viability and functional performance when grown as spheroids. Multicellular spheroids in this aspect are ideal building units for tissue reconstruction. Here we review the current understanding of multicellular spheroid formation mechanisms, their biomedical applications, and recent advances in spheroid culture, manipulation, and analysis techniques.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Previous studies have initiated spheroid experiments on day 7 due to a change in cellular structure from loose aggregate to spheroid.
“Previous studies have initiated spheroid experiments (eg. exposure) on day 7 (in both aquatic and mammalian based spheroids), due to a change in cellular structure from loose aggregate to spheroid [2, 11].”
From Direct Measurements of Oxygen Gradients in Spheroid Culture System Using Electron Parametric Resonance Oximetry (2016) · cites this paper as [11]
Cites
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 · see citing works
Optical Sectioning Deep Inside Live Embryos by Selective Plane Illumination Microscopy
Huisken, J., Swoger, J., Bene, F. D., Wittbrodt, J., & Stelzer, E. H. K. (2004) · Science · doi:10.1126/science.1100035 · Cited by 2,370 · see citing works
Capturing complex 3D tissue physiology in vitro
Griffith, L. G., & Swartz, M. A. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1858 · Cited by 2,274 · see citing works
Microscale technologies for tissue engineering and biology
Khademhosseini, A., Langer, R., Borenstein, J. T., & Vacanti, J. P. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507681102 · Cited by 1,553 · see citing works
Cell adhesion and signalling by cadherins and Ig-CAMs in cancer
Cavallaro, U., & Christofori, G. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1276 · Cited by 1,314 · see citing works
Organ printing: computer-aided jet-based 3D tissue engineering
Mironov, V., Boland, T., Trusk, T. C., Forgács, G., & Markwald, R. R. (2003) · Trends in biotechnology · doi:10.1016/s0167-7799(03)00033-7 · Cited by 1,278 · see citing works
Multiphoton microscopy in life sciences
König, K. (2000) · Journal of Microscopy · doi:10.1046/j.1365-2818.2000.00738.x · Cited by 1,265 · see citing works
Abbott, A. (2003) · Nature · doi:10.1038/424870a · Cited by 1,237 · see citing works
Optical Projection Tomography as a Tool for 3D Microscopy and Gene Expression Studies
Sharpe, J. A., Ahlgren, U., Perry, P., Hill, B., Ross, A., Hecksher‐Sørensen, J., Baldock, R., & Davidson, D. R. (2002) · Science · doi:10.1126/science.1068206 · Cited by 1,158 · see citing works
In vivo visualization of gene expression using magnetic resonance imaging
Louie, A. Y., Hüber, M. M., Ahrens, E. T., Rothbächer, U., Moats, R. A., Jacobs, R. E., Fraser, S. E., & Meade, T. J. (2000) · Nature Biotechnology · doi:10.1038/73780 · Cited by 1,132 · see citing works
Kelm, J. M., Timmins, N. E., Brown, C. J., Fussenegger, M., & Nielsen, L. K. (2003) · Biotechnology and Bioengineering · doi:10.1002/bit.10655 · Cited by 934 · see citing works
The use of 3-d cultures for high-throughput screening: the multicellular spheroid model.
Kunz-Schughart, L. A., Freyer, J. P., Hofstaedter, F., & Ebner, R. (2004) · SLAS DISCOVERY · doi:10.1177/1087057104265040 · Cited by 797 · see citing works
Weaver, V. M., Lelièvre, S. A., Lakins, J. N., Chrenek, M. A., Jones, J., Giancotti, F. G., Werb, Z., & Bissell, M. J. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00125-3 · Cited by 794 · see citing works
Application of inkjet printing to tissue engineering
Boland, T., Xu, T., Damon, B. J., & Cui, X. (2006) · Biotechnology Journal · doi:10.1002/biot.200600081 · Cited by 784 · see citing works
Sansone, P., Storci, G., Tavolari, S., Guarnieri, T., Giovannini, C., Taffurelli, M., Ceccarelli, C., Santini, D., Paterini, P., Marcu, K. B., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32533 · Cited by 779 · see citing works
Debnath, J., Mills, K. R., Collins, N. L., Reginato, M. J., Muthuswamy, S. K., & Brugge, J. S. (2002) · Cell · doi:10.1016/s0092-8674(02)01001-2 · Cited by 763 · see citing works
Demetriou, A. A., Brown, R. S., Busuttil, R. W., Fair, J. H., McGuire, B. M., Rosenthal, P. J., Esch, J. S. A., Lerut, J. P., Nyberg, S. L., Salizzoni, M., et al. (2004) · Annals of Surgery · doi:10.1097/01.sla.0000124298.74199.e5 · Cited by 670 · see citing works
Microfluidic scaffolds for tissue engineering
Choi, N., Cabodi, M., Held, B., Gleghorn, J. P., Bonassar, L. J., & Stroock, A. D. (2007) · Nature Materials · doi:10.1038/nmat2022 · Cited by 618 · see citing works
Three-dimensional tissue culture models in cancer biology
Kim, J. B. (2005) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2005.05.002 · Cited by 613 · see citing works
Building epithelial architecture: insights from three-dimensional culture models
O'Brien, L. E., Zegers, M. M. P., & Mostov, K. E. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm859 · Cited by 596 · see citing works
Korff, T., & Augustin, H. G. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.5.1341 · Cited by 561 · see citing works
Landry, J., Bernier, D., Ouellet, C., Goyette, R., & Marceau, N. (1985) · The Journal of Cell Biology · doi:10.1083/jcb.101.3.914 · Cited by 518 · see citing works
A simplified method for production and growth of multicellular tumor spheroids.
Yuhas, J. M., Li, A. P., Martinez, A. O., & Ladman, A. J. (1977) · PubMed · Cited by 506 · see citing works
The dissociation and aggregation of cells from organ rudiments of the early chick embryo.
(1952) · Europe PMC (PubMed Central) · Cited by 414 · see citing works
Engineering biological structures of prescribed shape using self-assembling multicellular systems
Jakab, K., Neagu, A., Mironov, V. A., Markwald, R. R., & Forgács, G. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400164101 · Cited by 394 · see citing works
Growing tissues in microgravity
Unsworth, B. R., & Lelkes, P. I. (1998) · Nature Medicine · doi:10.1038/nm0898-901 · Cited by 393 · see citing works
A Multiscale Model for Avascular Tumor Growth
Jiang, Y., Pješivac–Grbović, J., Cantrell, C., & Freyer, J. P. (2005) · Biophysical Journal · doi:10.1529/biophysj.105.060640 · Cited by 374 · see citing works
Preparation of alginate/galactosylated chitosan scaffold for hepatocyte attachment
Chung, T. W., Yang, J., Akaike, T., Cho, K. Y., Nah, J. W., Kim, S. I., & Cho, C. S. (2002) · Biomaterials · doi:10.1016/s0142-9612(01)00399-4 · Cited by 371 · see citing works
Controlling size, shape and homogeneity of embryoid bodies using poly(ethylene glycol) microwells
Karp, J. M., Yeh, J., Eng, G. M., Fukuda, J., Blumling, J., Suh, K. Y., Cheng, J., Mahdavi, A., Borenstein, J. T., Langer, R., et al. (2007) · Lab on a Chip · doi:10.1039/b705085m · Cited by 368 · see citing works
Korff, T., Kimmina, S., Martiny‐Baron, G., & Augustin, H. G. (2001) · The FASEB Journal · doi:10.1096/fj.00-0139com · Cited by 367 · see citing works
A study of the mechanics of gastrulation
Holtfreter, J. (1944) · Journal of Experimental Zoology · doi:10.1002/jez.1400950203 · Cited by 358 · see citing works
Micromolding of photocrosslinkable chitosan hydrogel for spheroid microarray and co-cultures
Fukuda, J., Khademhosseini, A., Yeo, Y., Yang, X., Yeh, J., Eng, G. M., Blumling, J., Wang, C.-F., Kohane, D. S., & Langer, R. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.05.044 · Cited by 334 · see citing works
Semino, C. E., Merok, J. R., Crane, G. G., Panagiotakos, G., & Zhang, S. (2003) · Differentiation · doi:10.1046/j.1432-0436.2003.7104503.x · Cited by 319 · see citing works
Cell Culture on a Thermo-Responsive Polymer Surface
Takezawa, T., Mori, Y., & Yoshizato, K. (1990) · Nature Biotechnology · doi:10.1038/nbt0990-854 · Cited by 310 · see citing works
Dynamic analysis of hepatoma spheroid formation: roles of E-cadherin and β1-integrin
Lin, R.-Z., Chou, L.-F., Chien, C.-C. M., & Chang, H.-Y. (2006) · Cell and Tissue Research · doi:10.1007/s00441-005-0148-2 · Cited by 305 · see citing works
Self-citationMicroscale tissue engineering using gravity-enforced cell assembly
Kelm, J. M., & Fussenegger, M. (2004) · Trends in biotechnology · doi:10.1016/j.tibtech.2004.02.002 · Cited by 296 · see citing works
Microfluidic self-assembly of tumor spheroids for anticancer drug discovery
Wu, L. Y., Carlo, D. D., & Lee, L. P. (2007) · Biomedical Microdevices · doi:10.1007/s10544-007-9125-8 · Cited by 268 · see citing works
Curcio, E., Salerno, S., Barbieri, G., Bartolo, L. D., Drioli, E., & Bader, A. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.08.033 · Cited by 262 · see citing works
Stable immobilization of rat hepatocyte spheroids on galactosylated nanofiber scaffold
Chua, K. N., Lim, W. S., Zhang, P., Lu, H., Wen, J., Ramakrishna, S., Leong, K. W., & Mao, H. (2004) · Biomaterials · doi:10.1016/j.biomaterials.2004.07.040 · Cited by 258 · see citing works
Micromolding of photocrosslinkable hyaluronic acid for cell encapsulation and entrapment
Khademhosseini, A., Eng, G. M., Yeh, J., Fukuda, J., Blumling, J., Langer, R., & Burdick, J. A. (2006) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30821 · Cited by 236 · see citing works
3-D microwell culture of human embryonic stem cells
Mohr, J. C., de Pablo, J. J., & Palecek, S. P. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.07.012 · Cited by 234 · see citing works
Structural Polarity and Functional Bile Canaliculi in Rat Hepatocyte Spheroids
Abu-Absi, S. F., Friend, J. R., Hansen, L. K., & Hu, W. (2002) · Experimental Cell Research · doi:10.1006/excr.2001.5467 · Cited by 230 · see citing works
Diversity of cell-mediated adhesions in breast cancer spheroids
Ivascu, A., & Kubbies, M. (2007) · International Journal of Oncology · doi:10.3892/ijo.31.6.1403 · Cited by 229 · see citing works
Dynamics of the Self-Assembly of Complex Cellular Aggregates on Micromolded Nonadhesive Hydrogels
Napolitano, A. P., Chai, P., Dean, D. M., & Morgan, J. R. (2007) · Tissue Engineering · doi:10.1089/ten.2006.0190 · Cited by 228 · see citing works
Ingram, M., Techy, G. B., Saroufeem, R. M. G., Yazan, O., Narayan, K. S., Goodwin, T. J., & Spaulding, G. F. (1997) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-997-0064-8 · Cited by 225 · see citing works
Hamer, P. C. D. W., van Tilborg, A. A. G., Eijk, P. P., Sminia, P., Troost, D., Noorden, C. J. F. V., Ylstra, B., & Leenstra, S. (2007) · Oncogene · doi:10.1038/sj.onc.1210850 · Cited by 216 · see citing works
Khademhosseini, A., Ferreira, L., Blumling, J., Yeh, J., Karp, J. M., Fukuda, J., & Langer, R. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.06.035 · Cited by 202 · see citing works
Hanging-drop multicellular spheroids as a model of tumour angiogenesis
Timmins, N., Dietmair, S., & Nielsen, L. K. (2004) · Angiogenesis · doi:10.1007/s10456-004-8911-7 · Cited by 177 · see citing works
A multicellular spheroid array to realize spheroid formation, culture, and viability assay on a chip
Torisawa, Y.-S., Takagi, A., Nashimoto, Y., Yasukawa, T., Shiku, H., & Matsue, T. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2006.08.054 · Cited by 176 · see citing works
Wartenberg, M., Dönmez, F., Ling, F. C., Acker, H., Hescheler, J., & Sauer, H. (2001) · The FASEB Journal · doi:10.1096/fj.00-0350com · Cited by 173 · see citing works
Dean, D. M., Napolitano, A. P., Youssef, J., & Morgan, J. R. (2007) · The FASEB Journal · doi:10.1096/fj.07-8710com · Cited by 167 · see citing works
Fukuda, J., Sakai, Y., & Nakazawa, K. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.07.031 · Cited by 163 · see citing works
Microfabrication-based modulation of embryonic stem cell differentiation
Park, J., Cho, C. H., Parashurama, N., 李雅文, Francois Berthiaume, B., Toner, M., Tilles, A. W., & Yarmush, M. L. (2007) · Lab on a Chip · doi:10.1039/b704739h · Cited by 159 · see citing works
Design of Custom-Shaped Vascularized Tissues Using Microtissue Spheroids as Minimal Building Units
Kelm, J. M., Djonov, V., Ittner, L. M., Fluri, D. A., Born, W., Hoerstrup, S. P., & Fussenegger, M. (2006) · Tissue Engineering · doi:10.1089/ten.2006.12.2151 · Cited by 157 · see citing works
Cell patterning using magnetite nanoparticles and magnetic force
Ino, K., Itô, A., & Honda, H. (2007) · Biotechnology and Bioengineering · doi:10.1002/bit.21322 · Cited by 152 · see citing works
Assembly of multicellular constructs and microarrays of cells using magnetic nanowires
Monica TanaseCurrent address: Department o, Felton, E. J., Gray, D. S., Hultgren, A., Chen, C. S., & Reich, D. H. (2005) · Lab on a Chip · doi:10.1039/b500243e · Cited by 143 · see citing works
Nyberg, S. L., Hardin, J. A., Amiot, B. P., Argikar, U. A., Remmel, R. P., & Rinaldo, P. (2005) · Liver Transplantation · doi:10.1002/lt.20446 · Cited by 142 · see citing works
Mueller-Klieser, W. (1984) · Biophysical Journal · doi:10.1016/s0006-3495(84)84030-8 · Cited by 140 · see citing works
Two‐Dimensional Multiarray Formation of Hepatocyte Spheroids on a Microfabricated PEG‐Brush Surface
Otsuka, H., Hirano, A., Nagasaki, Y., Okano, T., Horiike, Y., & Kataoka, K. (2004) · ChemBioChem · doi:10.1002/cbic.200300822 · Cited by 140 · see citing works
Kunz‐Schughart, L. A., Heyder, P., Schroeder, J. A., & Knuechel, R. (2001) · Experimental Cell Research · doi:10.1006/excr.2001.5210 · Cited by 138 · see citing works
Elkayam, T., Amitay-Shaprut, S., Dvir‐Ginzberg, M., Harel, T., & Cohen, S. (2006) · Tissue Engineering · doi:10.1089/ten.2006.12.1357 · Cited by 130 · see citing works
Design of Artificial Myocardial Microtissues
Kelm, J. M., Ehler, E., Nielsen, L. K., Schlatter, S., Perriard, J., & Fussenegger, M. (2004) · Tissue Engineering · doi:10.1089/107632704322791853 · Cited by 128 · see citing works
Relations between ph, oxygen partial pressure and growth in cultured cell spheroids
Carlsson, J., & Acker, H. (1988) · International Journal of Cancer · doi:10.1002/ijc.2910420515 · Cited by 127 · see citing works
Fibronectin Matrix Assembly Regulates α5β1-mediated Cell Cohesion
Robinson, E. E., Foty, R. A., & Corbett, S. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-07-0528 · Cited by 124 · see citing works
Spheroids in radiobiology and photodynamic therapy
Dubessy, C. (2000) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(00)00085-8 · Cited by 120 · see citing works
Mathematical modelling of drug transport in tumour multicell spheroids and monolayer cultures
Ward, J., & King, J. R. (2003) · Mathematical Biosciences · doi:10.1016/s0025-5564(02)00148-7 · Cited by 120 · see citing works
Lu, H., Chua, K. N., Zhang, P., Lim, W. S., Ramakrishna, S., Leong, K. W., & Mao, H. (2005) · Acta Biomaterialia · doi:10.1016/j.actbio.2005.04.003 · Cited by 118 · see citing works
Induction of three-dimensional assembly of human liver cells by simulated microgravity
Khaoustov, V. I., Darlington, G., Soriano, H. E., Krishnan, B., Risin, D., Pellis, N. R., & Yoffe, B. (1999) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-999-0060-2 · Cited by 114 · see citing works
The role of actin filaments and microtubules in hepatocyte spheroid self-assembly
Tzanakakis, E. S., Hansen, L. K., & Hu, W. (2001) · Cell Motility and the Cytoskeleton · doi:10.1002/1097-0169(200103)48:3 · Cited by 112 · see citing works
Takezawa, T., Yamazaki, M., Mori, Y., Yonaha, T., & Yoshizato, K. (1992) · Journal of Cell Science · doi:10.1242/jcs.101.3.495 · Cited by 110 · see citing works
Micropatterns of Matrigel for three-dimensional epithelial cultures
Sodunke, T. R., Turner, K. K., Caldwell, S. A., McBride, K. W., Reginato, M. J., & Noh, H. “. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.05.021 · Cited by 109 · see citing works
Extended liver-specific functions of porcine hepatocyte spheroids entrapped in collagen gel
Lazar, A., Mann, H. J., Remmel, R. P., Shatford, R. A. D., Cerra, F. B., & Hu, W. (1995) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/bf02634282 · Cited by 102 · see citing works
Dielectrophoresis based‐cell patterning for tissue engineering
Lin, R., Ho, C.-T., Liu, C., & Chang, H. (2006) · Biotechnology Journal · doi:10.1002/biot.200600112 · Cited by 101 · see citing works
Self-citationBrave Little World: Spheroids as an in vitro Model to Study Tumor-Immune-Cell Interactions
Gottfried, E., Kunz‐Schughart, L. A., Andreesen, R., & Kreutz, M. P. (2006) · Cell Cycle · doi:10.4161/cc.5.7.2624 · Cited by 91 · see citing works
Gondi, C. S., Lakka, S. S., Dinh, D. H., Olivero, W. C., Gujrati, M., & Rao, J. S. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-3032 · Cited by 91 · see citing works
Alvarez-Pérez, J., Ballesteros, P., & Cerdán, S. (2005) · Magnetic Resonance Materials in Physics Biology and Medicine · doi:10.1007/s10334-005-0013-z · Cited by 90 · see citing works
Gaedtke, L., Thoenes, L., Culmsee, C., Mayer, B., & Wagner, E. (2007) · Journal of Proteome Research · doi:10.1021/pr0700596 · Cited by 90 · see citing works
Moreno, J., Vargas, M. A., Madiedo, J. M., Muñoz, J., Rivas, J., & Guerrero, M. G. (2000) · Biotechnology and Bioengineering · doi:10.1002/(sici)1097-0290(20000205)67:3 · Cited by 90 · see citing works
Galactosylated PVDF membrane promotes hepatocyte attachment and functional maintenance
Lu, H., Lim, W. S., Wang, J., et al. (2003) · Biomaterials · doi:10.1016/s0142-9612(03)00404-6 · Cited by 89 · see citing works
Cell culture as spheroids: an approach to multicellular resistance.
Desoize, B., Gimonet, D., & Jardiller, J. C. (1999) · PubMed · Cited by 88 · see citing works
Jian, L., Kuznetsova, L. A., Edwards, G. O., Xu, J., Ma, M., Purcell, W. M., Jackson, S. K., & Coakley, W. T. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21345 · Cited by 83 · see citing works
Sebastian, A., Buckle, A., & Markx, G. H. (2007) · Biotechnology and Bioengineering · doi:10.1002/bit.21416 · Cited by 82 · see citing works
Characterization of Morphology and Cellular Metabolism during the Spheroid Formation by Fibroblasts
Takezawa, T., Mori, Y., Yonaha, T., & Yoshizato, K. (1993) · Experimental Cell Research · doi:10.1006/excr.1993.1265 · Cited by 77 · see citing works
Basal Caspase Activity Promotes Migration and Invasiveness in Glioblastoma Cells
Gdynia, G., Grund, K., Eckert, A., Böck, B. C., Funke, B., Macher‐Goeppinger, S., Sieber, S., Herold‐Mende, C. C., Wiestler, B., Wiestler, O. D., et al. (2007) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-07-0343 · Cited by 76 · see citing works
Wirz, W., Antoine, M., Tag, C. G., Gressner, A. M., Korff, T., Hellerbrand, C., & Kiefer, P. (2008) · Differentiation · doi:10.1111/j.1432-0436.2007.00260.x · Cited by 69 · see citing works
Wartenberg, M., Dönmez, F., Ling, F. C., et al. (2001) · The FASEB Journal · doi:10.1096/fsb2fj000350com · Cited by 69 · see citing works
Large-Scale Preparation and Function of Porcine Hepatocyte Spheroids
Sakai, Y., Naruse, K., Nagashima, I., Muto, T., & Suzuki, M. (1996) · The International Journal of Artificial Organs · doi:10.1177/039139889601900507 · Cited by 67 · see citing works
Qihao, Z., Xi-gu, C., Guanghui, C., & Weiwei, Z. (2007) · DNA and Cell Biology · doi:10.1089/dna.2006.0562 · Cited by 65 · see citing works
A multicellular spheroid-based sensor for anti-cancer therapeutics
Thielecke, H., Mack, A., & Robitzki, A. A. (2001) · Biosensors and Bioelectronics · doi:10.1016/s0956-5663(01)00140-3 · Cited by 63 · see citing works
Two-dimensional microarray of HepG2 spheroids using collagen/polyethylene glycol micropatterned chip
Tamura, T., Sakai, Y., & Nakazawa, K. (2007) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-007-3305-1 · Cited by 62 · see citing works
Dardousis, K., Voolstra, C., Roengvoraphoj, M., Sekandarzad, A., Mesghenna, S., Winkler, J., Ko, Y., Hescheler, J., & Sachinidis, A. (2006) · Molecular Therapy · doi:10.1038/sj.mt.6300003 · Cited by 55 · see citing works
Entrapment of Hepatocyte Spheroids in a Hollow Fiber Bioreactor as a Potential Bioartificial Liver
Wu, F. J., Peshwa, M. V., Cerra, F. B., & Hu, W. (1995) · Tissue Engineering · doi:10.1089/ten.1995.1.29 · Cited by 51 · see citing works
Seidl, P., Huettinger, R., Knuechel, R., & Kunz‐Schughart, L. A. (2002) · International Journal of Cancer · doi:10.1002/ijc.10675 · Cited by 50 · see citing works
Yamada, K., Kamihira, M., Hamamoto, R., et al. (1998) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a022037 · Cited by 50 · see citing works
Spatial Composition of Prostate Cancer Spheroids in Mixed and Static Cultures
Hong, S., David, O., Clejan, S., Giordano, C. L., LeBeau, H., Xu, L., & O’Connor, K. C. (2004) · Tissue Engineering · doi:10.1089/ten.2004.10.1266 · Cited by 48 · see citing works
Hu, G., & Li, D. (2007) · Biomedical Microdevices · doi:10.1007/s10544-006-9035-1 · Cited by 47 · see citing works
Autologous spheroid culture: a screening tool for human brain tumour invasion
DERIDDER, L. (2000) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(00)00081-0 · Cited by 45 · see citing works
Du, Y., Han, R., Ng, S., Ni, J., Sun, W., Wohland, T., Ong, S., Kuleshova, L. L., & Yu, H. (2007) · Tissue Engineering · doi:10.1089/ten.2006.0381 · Cited by 41 · see citing works
Periosteal Cell Pellet Culture System: A New Technique for Bone Engineering
Akiyama, M., Nonomura, H., Kamil, S. H., & Ignotz, R. A. (2006) · Cell Transplantation · doi:10.3727/000000006783981765 · Cited by 41 · see citing works
Török, É., Vogel, C., tgehetmann, M. L., Ma, P. X., Dandri, M., Petersen, J., Burda, M. R., Siebert, K., Düllmann, J., Rogiers, X., et al. (2006) · Tissue Engineering · doi:10.1089/ten.2006.12.1881 · Cited by 38 · see citing works
Accelerated formation of multicellular 3‐D structures by cell‐to‐cell cross‐linking
Bank, P. D., Hou, Q., Warner, R. M., Wood, I. V., Ali, B. E., MacNeil, S., Kendall, D. A., Kellam, B., Shakesheff, K. M., & Buttery, L. D. K. (2007) · Biotechnology and Bioengineering · doi:10.1002/bit.21343 · Cited by 38 · see citing works
Shimazui, T., Schalken, J. A., Kawai, K., Kawamoto, R., van Bockhoven, A., Oosterwijk, E., & Akaza, H. (2004) · Oncology Reports · doi:10.3892/or.11.2.357 · Cited by 37 · see citing works
Lin, K., Maeda, S., & Saito, T. (1995) · Biotechnology and Applied Biochemistry · doi:10.1111/j.1470-8744.1995.tb00325.x · Cited by 35 · see citing works
Spheroid Formation of Hepatocytes Using Synthetic Polymer
Kamihira, M., Yamada, K., Hamamoto, R., & Iijima, S. (1997) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1997.tb52213.x · Cited by 35 · see citing works
Spheroids: relation between tumour and endothelial cells
Oudar, O. (2000) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(00)00080-9 · Cited by 33 · see citing works
Monazzam, A., Josephsson, R., BLOMQVIST, C. P., Carlsson, J., Långström, B., & Bergström, M. (2007) · Breast Cancer Research · doi:10.1186/bcr1747 · Cited by 33 · see citing works
Matta, S. G., Wobken, J. D., Williams, F. G., et al. (1994) · PubMed · Cited by 31 · see citing works
Higashiyama, S., Noda, M., Kawase, M., et al. (2003) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.10419 · Cited by 30 · see citing works
Schuster, U., Büttner, R., Hofstädter, F., et al. (1994) · The Journal of Urology · doi:10.1016/s0022-5347(17)35349-1 · Cited by 30 · see citing works
Pancreatic Islet Cell Reaggregation Systems
Matta, S. G., Wobken, J. D., Williams, F. G., et al. (1994) · Pancreas · doi:10.1097/00006676-199407000-00005 · Cited by 30 · see citing works
Krubasik, D., Eisenach, P. A., Kunz‐Schughart, L. A., Murphy, G., & English, W. (2007) · International Journal of Cancer · doi:10.1002/ijc.23234 · Cited by 27 · see citing works
Differential gene expression analysis during porcine hepatocyte spheroid formation
Narayanan, R. A., Rink, A., Beattie, C. W., et al. (2002) · Mammalian Genome · doi:10.1007/s00335-002-2179-2 · Cited by 25 · see citing works
Ugele, B., & Lange, F. (2001) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1290/1071-2690(2001)037 · Cited by 24 · see citing works
Chapter 15 Digital Deconvolution of Fluorescence Images for Biologists
Wang, Y. (1998) · Methods in cell biology · doi:10.1016/s0091-679x(08)60432-x · Cited by 22 · see citing works
Formation of multicellular spheroids composed of rat hepatocytes.
Ueno, K., Miyashita, A., Endoh, E., Takezawa, T., Yamazaki, M., Mori, Y., & Satoh, T. (1992) · PubMed · Cited by 21 · see citing works
Huang, S., Vader, D., Wang, Z., et al. (2008) · BMC Medical Imaging · doi:10.1186/1471-2342-8-3 · Cited by 20 · see citing works
Lee, K.-W., Lee, S. K., Joh, J., Kim, S. J., Lee, B.-B., Kim, K.-W., & Lee, K. U. (2004) · Tissue Engineering · doi:10.1089/ten.2004.10.965 · Cited by 19 · see citing works
Identification of three gene candidates for multicellular resistance in colon carcinoma
Timmins, N. E., Maguire, T. L., Grimmond, S. M., & Nielsen, L. K. (2004) · Cytotechnology · doi:10.1007/s10616-005-1476-5 · Cited by 18 · see citing works
Teratani, T., Quinn, G., Yamamoto, Y., Sato, T., Yamanokuchi, H., Asari, A., & Ochiya, T. (2005) · Cell Transplantation · doi:10.3727/000000005783982611 · Cited by 18 · see citing works
Haga, T., Uchide, N., Tugizov, S. M., & Palefsky, J. M. (2007) · APOPTOSIS · doi:10.1007/s10495-007-0132-2 · Cited by 17 · see citing works
Murakami, S., Ijima, H., Ono, T., & Kawakami, K. (2004) · The International Journal of Artificial Organs · doi:10.1177/039139880402700207 · Cited by 16 · see citing works
Santini, M. T., Romano, R., Rainaldi, G., et al. (2006) · Radiation Research · doi:10.1667/rr0635.1 · Cited by 14 · see citing works
Lincz, L. F., Burns, G. F., & Buret, A. G. (1997) · Differentiation · doi:10.1046/j.1432-0436.1997.6140261.x · Cited by 13 · see citing works
Gwak, S., Choi, D., Paik, S. S., Cho, S., Kim, S. S., Choi, C. Y., & Kim, B. (2006) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30687 · Cited by 12 · see citing works
Hybrid spheroids as a tool for prediction of radiosensitivity in tumor therapy.
Djordjevic, B., & Lange, C. S. (2004) · PubMed · Cited by 6 · see citing works
Ota, K., Saito, S., Hamasaki, K., et al. (1996) · PubMed · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Edmondson, R., Broglie, J. J., Adcock, A. F., & Yang, L. (2014) · ASSAY and Drug Development Technologies · doi:10.1089/adt.2014.573 · Cited by 2,515 · see citing works
Is it time to start transitioning from 2D to 3D cell culture?
Jensen, C., & Teng, Y. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.00033 · Cited by 1,640 · see citing works
Three-dimensional cell culture: the missing link in drug discovery
Breslin, S., & O’Driscoll, L. (2013) · Drug Discovery Today · doi:10.1016/j.drudis.2012.10.003 · Cited by 1,332 · see citing works
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S., Bode, J. G., Bolleyn, J., Borner, C., Böttger, J., et al. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1078-5 · Cited by 1,280 · see citing works
Organ printing: Tissue spheroids as building blocks
Mironov, V., Visconti, R. P., Kasyanov, V., Forgacs, G., Drake, C. J., & Markwald, R. R. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2008.12.084 · Cited by 1,238 · see citing works
Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy
Mehta, G., Hsiao, A. Y., Ingram, M., Luker, G. D., & Takayama, S. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.04.045 · Cited by 1,172 · see citing works
Spheroid culture as a tool for creating 3D complex tissues
Fennema, E., Rivron, N., Rouwkema, J., van Blitterswijk, C., & de Boer, J. (2013) · Trends in Biotechnology · doi:10.1016/j.tibtech.2012.12.003 · Cited by 1,054 · see citing works
Three-dimensional culture systems in cancer research: Focus on tumor spheroid model
Nath, S., & Devi, G. R. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.03.013 · Cited by 919 · see citing works
Bell, C. C., Hendriks, D. F. G., Moro, S. M. L., Ellis, E., Walsh, J., Renblom, A., Fredriksson Puigvert, L., Dankers, A. C. A., Jacobs, F., Snoeys, J., et al. (2016) · Scientific Reports · doi:10.1038/srep25187 · Cited by 739 · see citing works
In Vitro Tumor Models: Advantages, Disadvantages, Variables, and Selecting the Right Platform
Katt, M. E., Placone, A. L., Wong, A. D., Xu, Z. S., & Searson, P. C. (2016) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2016.00012 · Cited by 754 · see citing works
Spheroid Culture of Mesenchymal Stem Cells
Cesarz, Z., & Tamama, K. (2016) · Stem Cells International · doi:10.1155/2016/9176357 · Cited by 475 · see citing works
Hoarau-Véchot, J., Rafii, A., Touboul, C., & Pasquier, J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010181 · Cited by 489 · see citing works
Bioprinting Technology: A Current State-of-the-Art Review
Dababneh, A. B., & Ozbolat, I. T. (2014) · Journal of Manufacturing Science and Engineering · doi:10.1115/1.4028512 · Cited by 427 · see citing works
Microfluidic system for formation of PC-3 prostate cancer co-culture spheroids
Hsiao, A. Y., Torisawa, Y.-S., Tung, Y.-C., Sud, S., Taichman, R. S., Pienta, K. J., & Takayama, S. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.02.047 · Cited by 323 · see citing works
Engineering cancer microenvironments for in vitro 3-D tumor models
Asghar, W., El Assal, R., Shafiee, H., Pitteri, S., Paulmurugan, R., & Demirci, U. (2015) · Materials Today · doi:10.1016/j.mattod.2015.05.002 · Cited by 316 · see citing works
Barrila, J., Radtke, A. L., Crabbé, A., Sarker, S. F., Herbst-Kralovetz, M. M., Ott, C. M., & Nickerson, C. A. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2423 · Cited by 302 · see citing works
3D Organotypic Cultures of Human HepaRG Cells: A Tool for In Vitro Toxicity Studies
Gunness, P., Mueller, D., Shevchenko, V., Heinzle, E., Ingelman-Sundberg, M., & Noor, F. (2013) · Toxicological Sciences · doi:10.1093/toxsci/kft021 · Cited by 236 · see citing works
Dynamics of the Self-Assembly of Complex Cellular Aggregates on Micromolded Nonadhesive Hydrogels
Napolitano, A. P., Chai, P., Dean, D. M., & Morgan, J. R. (2007) · Tissue Engineering · doi:10.1089/ten.2006.0190 · Cited by 228 · see citing works
Costa, E. C., de Melo‐Diogo, D., Moreira, A. F., Carvalho, M. P., & Correia, I. J. (2018) · Biotechnology Journal · doi:10.1002/biot.201700417 · Cited by 224 · see citing works
Towards organ printing: engineering an intra-organ branched vascular tree
Visconti, R. P., Kasyanov, V., Gentile, C., Zhang, J., Markwald, R. R., & Mironov, V. (2010) · Expert Opinion on Biological Therapy · doi:10.1517/14712590903563352 · Cited by 224 · see citing works
Patra, B., Peng, C.-C., Liao, W.-H., Lee, C.-H., & Tung, Y.-C. (2016) · Scientific Reports · doi:10.1038/srep21061 · Cited by 215 · see citing works
3D tumor models: History, advances and future perspectives
Benien, P., & Swami, A. (2014) · Future Oncology · doi:10.2217/fon.13.274 · Cited by 208 · see citing works
Yoon No, D., Lee, K.-H., Lee, J., & Lee, S.-H. (2015) · Lab on a Chip · doi:10.1039/c5lc00611b · Cited by 205 · see citing works
Competency of different cell models to predict human hepatotoxic drugs
Gómez-Lechón, M. J., Tolosa, L., Conde, I., & Donato, M. T. (2014) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2014.967680 · Cited by 199 · see citing works
Santos, J. M., Camões, S. P., Filipe, E., Cipriano, M., Barcia, R. N., Filipe, M., Teixeira, M., Simões, S., Gaspar, M., Mosqueira, D., et al. (2015) · Stem Cell Research & Therapy · doi:10.1186/s13287-015-0082-5 · Cited by 196 · see citing works
Vörsmann, H., Groeber, F., Walles, H., Busch, S., Beissert, S., Walczak, H., & Kulms, D. (2013) · Cell Death & Disease · doi:10.1038/cddis.2013.249 · Cited by 168 · see citing works
“Only spheroids with sizes of/above 500mm represent typical features of nonvascularized tumor tissue.(16,31) To date, conventional chemotherapy-based cancer treat-”
BackgroundOptimization of liquid overlay technique to formulate heterogenic 3D co-cultures models
Costa, E. C., Gaspar, V. M., Coutinho, P., & Correia, I. J. (2014) · Biotechnology and Bioengineering · doi:10.1002/bit.25210 · Cited by 156 · see citing works
Tumor cells and their crosstalk with endothelial cells in 3D spheroids
Shoval, H., Karsch-Bluman, A., Brill-Karniely, Y., Stern, T., Zamir, G., Hubert, A., & Benny, O. (2017) · Scientific Reports · doi:10.1038/s41598-017-10699-y · Cited by 138 · see citing works
On being the right size: scaling effects in designing a human-on-a-chip
Moraes, C., Labuz, J. M., Leung, B. M., Inoue, M., Chun, T.-H., & Takayama, S. (2013) · Integrative Biology · doi:10.1039/c3ib40040a · Cited by 134 · see citing works
Li, C. Y., Stevens, K. R., Schwartz, R. E., Alejandro, B. S., Huang, J. H., & Bhatia, S. N. (2014) · Tissue Engineering Part A · doi:10.1089/ten.tea.2013.0667 · Cited by 132 · see citing works
Hsiao, A. Y., Tung, Y.-C., Kuo, C.-H., Mosadegh, B., Bedenis, R., Pienta, K. J., & Takayama, S. (2012) · Biomedical Microdevices · doi:10.1007/s10544-011-9608-5 · Cited by 129 · see citing works
Polysaccharide matrices used in 3D in vitro cell culture systems
Diekjürgen, D., & Grainger, D. W. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.06.020 · Cited by 125 · see citing works
3D Bioprinting of Tumor Models for Cancer Research
Kang, Y., Datta, P., Shanmughapriya, S., & Ozbolat, I. T. (2020) · ACS Applied Bio Materials · doi:10.1021/acsabm.0c00791 · Cited by 112 · see citing works
Ho, W. J., Pham, E. A., Kim, J. W., Ng, C. W., Kim, J. H., Kamei, D. T., & Wu, B. M. (2010) · Cancer Science · doi:10.1111/j.1349-7006.2010.01723.x · Cited by 115 · see citing works
Patra, B., Chen, Y.-H., Peng, C.-C., Lin, S.-C., Lee, C.-H., & Tung, Y.-C. (2013) · Biomicrofluidics · doi:10.1063/1.4824480 · Cited by 109 · see citing works
Yeon, S.-E., No, D. Y., Lee, S.-H., Nam, S. W., Oh, I.-H., Lee, J., & Kuh, H.-J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073345 · Cited by 110 · see citing works
Langan, L. M., Dodd, N. J. F., Owen, S. F., Purcell, W. M., Jackson, S. K., & Jha, A. N. (2016) · PLOS ONE · doi:10.1371/journal.pone.0149492 · Cited by 101 · see citing works
Sun, Q., Tan, S. H., Chen, Q., Ran, R., Hui, Y., Chen, D., & Zhao, C.-X. (2018) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.8b00904 · Cited by 100 · see citing works
Toward the broad adoption of 3D tumor models in the cancer drug pipeline
Cox, M. C., Reese, L. M., Bickford, L. R., & Verbridge, S. S. (2015) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.5b00172 · Cited by 80 · see citing works
Uniform Beads with Controllable Pore Sizes for Biomedical Applications
Choi, S., Yeh, Y., Zhang, Y., Sung, H., & Xia, Y. (2010) · Small · doi:10.1002/smll.201000544 · Cited by 81 · see citing works
Bauleth-Ramos, T., Feijão, T., Gonçalves, A., Shahbazi, M.-A., Liu, Z., Barrias, C., Oliveira, M. J., Granja, P., Santos, H. A., & Sarmento, B. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.04.025 · Cited by 79 · see citing works
Huang, K., Boerhan, R., Liu, C., & Jiang, G. (2017) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.7b00726 · Cited by 74 · see citing works
Damania, A., Kumar, A., Teotia, A. K., Kimura, H., Kamihira, M., Ijima, H., Sarin, S. K., & Kumar, A. (2018) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b13727 · Cited by 71 · see citing works
Three-Dimensional Breast Cancer Models Mimic Hallmarks of Size-Induced Tumor Progression
Singh, M., Mukundan, S., Jaramillo, M., Oesterreich, S., & Sant, S. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2304 · Cited by 68 · see citing works
Engineering Liver Microtissues for Disease Modeling and Regenerative Medicine
Huang, D. (., Gibeley, S. B., Xu, C., Xiao, Y., Celik, O., Ginsberg, H. N., & Leong, K. W. (2020) · Advanced Functional Materials · doi:10.1002/adfm.201909553 · Cited by 65 · see citing works
Kim, T. Y., Kofron, C. M., King, M. E., Markes, A. R., Okundaye, A. O., Qu, Z., Mende, U., & Choi, B.-R. (2018) · PLOS ONE · doi:10.1371/journal.pone.0196714 · Cited by 57 · see citing works
Lee, B. H., Shirahama, H., Kim, M. H., Lee, J. H., Cho, N.-J., & Tan, L. P. (2017) · NPG Asia Materials · doi:10.1038/am.2017.126 · Cited by 52 · see citing works
Progress in melanoma modelling in vitro
Marconi, A., Quadri, M., Saltari, A., & Pincelli, C. (2018) · Experimental Dermatology · doi:10.1111/exd.13670 · Cited by 51 · see citing works
Voissiere, A., Jouberton, E., Maubert, E., Degoul, F., Peyrode, C., Chezal, J.-M., & Miot-Noirault, É. (2017) · PLOS ONE · doi:10.1371/journal.pone.0181340 · Cited by 49 · see citing works
Wang, J.-Z., Zhu, Y.-X., Ma, H.-C., Chen, S.-N., Chao, J.-Y., Ruan, W.-D., Wang, D., Du, F.-G., & Meng, Y.-Z. (2016) · Materials Science and Engineering: C · doi:10.1016/j.msec.2016.01.045 · Cited by 49 · see citing works
Networked concave microwell arrays for constructing 3D cell spheroids
Lee, G. H., Lee, J. S., Lee, G.-H., Joung, W. Y., Kim, S. H., Lee, S. H., Park, J. Y., & Kim, D.-H. (2018) · Biofabrication · doi:10.1088/1758-5090/aa9876 · Cited by 47 · see citing works
Li, G., He, J., Shi, J., Li, X., Liu, L., Ge, X., Chen, W., Jia, J., Wang, J., Yin, M., et al. (2025) · Gut · doi:10.1136/gutjnl-2024-333885 · Cited by 41 · see citing works
Xia, Y., Chen, H., Li, J., Hu, H., Qian, Q., He, R.-X., Ding, Z., & Guo, S.-S. (2021) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.1c06655 · Cited by 35 · see citing works
3D Tumor Spheroid Models for In Vitro Therapeutic Screening of Nanoparticles
Daunys, S., Janonienė, A., Januškevičienė, I., Paškevičiūtė, M., & Petrikaitė, V. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-58174-9_11 · Cited by 32 · see citing works
Avnet, S., Lemma, S., Cortini, M., Di Pompo, G., Perut, F., & Baldini, N. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00305 · Cited by 29 · see citing works
A spheroid-based biosensor for the label-free detection of drug-induced field potential alterations
Daus, A. W., Layer, P. G., & Thielemann, C. (2012) · Sensors and Actuators B: Chemical · doi:10.1016/j.snb.2012.02.011 · Cited by 23 · see citing works
Fabrication of micro-cages and caged tumor spheroids for microfluidic chip-based assays
He, Y., Huang, B., Rofaani, E., Hu, J., Liu, Y., Pitingolo, G., Wang, L., Shi, J., Aimé, C., & Chen, Y. (2020) · Microelectronic Engineering · doi:10.1016/j.mee.2020.111256 · Cited by 13 · see citing works
Boussommier-Calleja, A. (2020) · Bioengineering Innovative Solutions for Cancer · doi:10.1016/b978-0-12-813886-1.00013-9 · Cited by 10 · see citing works
- Authors
- Lin, R., & Chang, H.
- Affiliations
- National Tsing Hua University (TW)
- Corresponding author
- Chang, Hwan‐You
- ORCID
- Chang, Hwan‐You
- Venue
- Biotechnology Journal
- Publisher
- Wiley
- Published
- 2008-10
- Volume
- 3
- Issue
- 9-10
- Pages
- 1172-1184
- ISSN
- 1860-6768 (ISSN-L)
- 1860-7314
- OpenAlex
- W1981684516
- Cited by
- 1,264
- References
- 126
- Citations by year
- 2026: 44 · 2025: 73 · 2024: 70 · 2023: 63 · 2022: 88 · 2021: 103 · 2020: 103 · 2019: 95 · 2018: 105 · 2017: 103 · 2016: 97 · 2015: 64 · 2014: 63 · 2013: 64 · 2012: 37
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biotechnology Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- multicellular spheroids, 3D cell culture, metastasis, tumor invasion, therapeutic screening, primary cells, progenitor cells, tissue reconstruction
- MeSH terms
- Animals, Cell Movement, Humans, Models, Biological, Tumor Cells, Cultured, Spheroids, Cellular, Cell Culture Techniques, Tissue Engineering, Biomedical Research
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