Three-Dimensional Cell Cultures in Drug Discovery and Development

Hallmarks of Cancer: The Next Generation

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Matrix elasticity directs stem cell lineage specification

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The origins and the future of microfluidics

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3D bioprinting of tissues and organs

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Cerebral organoids model human brain development and microcephaly

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Reconstituting organ-level lung functions on a chip

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Can the pharmaceutical industry reduce attrition rates?

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Tensional homeostasis and the malignant phenotype

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How to improve R&D productivity: the pharmaceutical industry's grand challenge

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Organoid Models and Applications in Biomedical Research

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Microfluidic organs-on-chips

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Taking Cell-Matrix Adhesions to the Third Dimension

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Organogenesis in a dish: Modeling development and disease using organoid technologies

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Principles of early drug discovery

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Hydrogels as extracellular matrix mimics for 3D cell culture

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Three-Dimensional Scaffolds for Tissue Engineering Applications: Role of Porosity and Pore Size

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Clinical development success rates for investigational drugs

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Vascularized and functional human liver from an iPSC-derived organ bud transplant

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Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues

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Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro

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Tissue-engineered autologous bladders for patients needing cystoplasty

Atala, A., Bauer, S. B., Söker, S., Yoo, J. J., & Retik, A. B. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68438-9 · Cited by 1,835 · see citing works

From 3D cell culture to organs-on-chips

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How were new medicines discovered?

Swinney, D. C., & Anthony, J. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3480 · Cited by 1,812 · see citing works

Modeling Tissue Morphogenesis and Cancer in 3D

Yamada, K. M., & Cukierman, E. (2007) · Cell · doi:10.1016/j.cell.2007.08.006 · Cited by 1,751 · see citing works

Photopolymerizable hydrogels for tissue engineering applications

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Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis

Takasato, M., Er, P. X., Chiu, H. S., Maier, B., Baillie, G. J., Ferguson, C., Parton, R. G., Wolvetang, E. J., Roost, M. S., Chuva de Sousa Lopes, S. M., et al. (2015) · Nature · doi:10.1038/nature15695 · Cited by 1,627 · see citing works

In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration

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Microscale technologies for tissue engineering and biology

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Lgr5+ve Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro

Barker, N., Huch, M., Kujala, P., van de Wetering, M., Snippert, H. J., van Es, J. H., Sato, T., Stange, D. E., Begthel, H., van den Born, M., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2009.11.013 · Cited by 1,547 · see citing works

Synthetic Matrix Metalloproteinase-Sensitive Hydrogels for the Conduction of Tissue Regeneration: Engineering Cell-Invasion Characteristics

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Organoids as an in vitro model of human development and disease

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Self-formation of optic cups and storable stratified neural retina from human ESCs

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Scaffold-free vascular tissue engineering using bioprinting

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Three-dimensional cell culture: the missing link in drug discovery

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Organ printing: Tissue spheroids as building blocks

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Organs-on-chips at the frontiers of drug discovery

Esch, E. W., Bahinski, A., & Huh, D. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4539 · Cited by 1,185 · see citing works

Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy

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Spherical Cancer Models in Tumor Biology

Weiswald, L., Bellet, D. H., & Dangles‐Marie, V. (2015) · Neoplasia · doi:10.1016/j.neo.2014.12.004 · Cited by 1,138 · see citing works

Modeling colorectal cancer using CRISPR-Cas9–mediated engineering of human intestinal organoids

Matano, M., Date, S., Shimokawa, M., Takano, A., Fujii, M., Ohta, Y., Watanabe, T., Kanai, T., & Sato, T. (2015) · Nature Medicine · doi:10.1038/nm.3802 · Cited by 1,135 · see citing works

Printing and Prototyping of Tissues and Scaffolds

Derby, B. (2012) · Science · doi:10.1126/science.1226340 · Cited by 1,108 · see citing works

Sequential cancer mutations in cultured human intestinal stem cells

Drost, J., van Jaarsveld, R. H., Ponsioen, B., Zimberlin, C., van Boxtel, R., Buijs, A., Sachs, N., Overmeer, R. M., Offerhaus, G. J., Begthel, H., et al. (2015) · Nature · doi:10.1038/nature14415 · Cited by 1,067 · see citing works

Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation

Vinci, M., Gowan, S., Boxall, F., Patterson, L., Zimmermann, M., Court, W., Lomas, C., Mendiola, M., Hardisson, D., & Eccles, S. A. (2012) · BMC Biology · doi:10.1186/1741-7007-10-29 · Cited by 1,024 · see citing works

The 3D printing of gelatin methacrylamide cell-laden tissue-engineered constructs with high cell viability

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A functional CFTR assay using primary cystic fibrosis intestinal organoids

Dekkers, J. F., Wiegerinck, C. L., de Jonge, H. R., Bronsveld, I., Janssens, H. M., de Winter-de Groot, K. M., Brandsma, A. M., de Jong, N. W. M., Bijvelds, M. J. C., Scholte, B. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3201 · Cited by 999 · see citing works

A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice

Huh, D., Leslie, D. C., Matthews, B. D., Fraser, J. P., Jurek, S., Hamilton, G. A., Thorneloe, K. S., McAlexander, M. A., & Ingber, D. E. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004249 · Cited by 993 · see citing works

High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array

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Materials as stem cell regulators

Murphy, W. L., McDevitt, T. C., & Engler, A. J. (2014) · Nature Materials · doi:10.1038/nmat3937 · Cited by 947 · see citing works

The productivity crisis in pharmaceutical R&D

Pammolli, F., Magazzini, L., & Riccaboni, M. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3405 · Cited by 918 · see citing works

Redefining the In Vivo Origin of Metanephric Nephron Progenitors Enables Generation of Complex Kidney Structures from Pluripotent Stem Cells

Taguchi, A., Kaku, Y., Ohmori, T., Sharmin, S., Ogawa, M., Sasaki, H., & Nishinakamura, R. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.11.010 · Cited by 871 · see citing works

Metre-long cell-laden microfibres exhibit tissue morphologies and functions

Onoe, H., Okitsu, T., Itou, A., Kato‐Negishi, M., Gojo, R., Kiriya, D., Sato, K., Miura, S., Iwanaga, S., Kuribayashi‐Shigetomi, K., et al. (2013) · Nature Materials · doi:10.1038/nmat3606 · Cited by 863 · see citing works

Trends in the exploitation of novel drug targets

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Hydrogel properties influence ECM production by chondrocytes photoencapsulated in poly(ethylene glycol) hydrogels

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Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells

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Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell

Yui, S., Nakamura, T., Sato, T., Nemoto, Y., Mizutani, T., Zheng, X., Ichinose, S., Nagaishi, T., Okamoto, R., Tsuchiya, K., et al. (2012) · Nature Medicine · doi:10.1038/nm.2695 · Cited by 805 · see citing works

Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids

Freedman, B., Brooks, C. R., Lam, A. Q., Fu, H., Morizane, R., Agrawal, V., Saad, A. F., Li, M. K., Hughes, M. R., Werff, R. V., et al. (2015) · Nature Communications · doi:10.1038/ncomms9715 · Cited by 785 · see citing works

Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease

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Three-dimensional organotypic culture: experimental models of mammalian biology and disease

Shamir, E. R., & Ewald, A. J. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3873 · Cited by 719 · see citing works

3D Bioprinting for Tissue and Organ Fabrication

Zhang, Y. S., Yue, K., Aleman, J., Mollazadeh‐Moghaddam, K., Bakht, S. M., Yang, J., Jia, W., Dell’Erba, V., Assawes, P., Shin, S. R., et al. (2016) · Annals of Biomedical Engineering · doi:10.1007/s10439-016-1612-8 · Cited by 695 · see citing works

Biodegradable Polymer Scaffolds with Well-Defined Interconnected Spherical Pore Network

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Gene 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 · see citing works

Growth of Multicell Spheroids in Tissue Culture as a Model of Nodular Carcinomas 2

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Modeling mouse and human development using organoid cultures

Huch, M., & Koo, B. (2015) · Development · doi:10.1242/dev.118570 · Cited by 543 · see citing works

Differentiated Troy+ Chief Cells Act as Reserve Stem Cells to Generate All Lineages of the Stomach Epithelium

Stange, D. E., Koo, B., Huch, M., Sibbel, G., Başak, O., Lyubimova, A., Kujala, P., Bartfeld, S., Köster, J., Geahlen, J. H., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.008 · Cited by 509 · see citing works

Lung Stem Cell Differentiation in Mice Directed by Endothelial Cells via a BMP4-NFATc1-Thrombospondin-1 Axis

Lee, J., Bhang, D. H., Beede, A. M., Huang, T. L., Stripp, B. R., Bloch, K. D., Wagers, A. J., Tseng, Y., Ryeom, S. W., & Kim, C. F. (2014) · Cell · doi:10.1016/j.cell.2013.12.039 · Cited by 491 · see citing works

Cancer stem cells from colorectal cancer-derived cell lines

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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

Tissue architecture: the ultimate regulator of breast epithelial function

Bissell, M. J., Rizki, A., & Mian, S. I. (2003) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2003.10.016 · Cited by 465 · see citing works

The mesenchymal stromal cells dilemma—does a negative phase III trial of random donor mesenchymal stromal cells in steroid-resistant graft-versus-host disease represent a death knell or a bump in the road?

Galipeau, J. (2013) · Cytotherapy · doi:10.1016/j.jcyt.2012.10.002 · Cited by 448 · see citing works

Perfused multiwell plate for 3D liver tissue engineering

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Three-dimensionally printed biological machines powered by skeletal muscle

Cvetkovic, C., Raman, R., Chan, V., Williams, B. J., Tolish, M., Bajaj, P., Sakar, M. S., Asada, H. H., Saif, M. T. A., & Bashir, R. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1401577111 · Cited by 442 · see citing works

Physiological function and transplantation of scaffold-free and vascularized human cardiac muscle tissue

Stevens, K. R., Kreutziger, K. L., Dupras, S. K., Korte, F. S., Regnier, M., Muskheli, V., Nourse, M. B., Bendixen, K., Reinecke, H., & Murry, C. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908381106 · Cited by 422 · see citing works

Emergence of Patterned Stem Cell Differentiation Within Multicellular Structures

Ruiz, S. A., & Chen, C. S. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0432 · Cited by 415 · see citing works

Transplantation of Expanded Fetal Intestinal Progenitors Contributes to Colon Regeneration after Injury

Fordham, R. P., Yui, S., Hannan, N. R. F., Soendergaard, C., Madgwick, A., Schweiger, P. J., Nielsen, O. H., Vallier, L., Pedersen, R. A., Nakamura, T., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.09.015 · Cited by 397 · see citing works

Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges

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Three‐dimensional models of cancer for pharmacology and cancer cell biology: Capturing tumor complexity in vitro/ex vivo

Hickman, J. A., Graeser, R., Hoogt, R. D., Vidic, S., Brito, C., Gutekunst, M., & van der Kuip, H. (2014) · Biotechnology Journal · doi:10.1002/biot.201300492 · Cited by 379 · see citing works

Fundamental studies of a novel, biodegradable PEG-b-PLA hydrogel

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Organotypic liver culture models: meeting current challenges in toxicity testing

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Generation of functional thyroid from embryonic stem cells

Antonica, F., Kasprzyk, D. F., Opitz, R., Iacovino, M., Liao, X.-H., Dumitrescu, A. M., Refetoff, S., Peremans, K., Manto, M., Kyba, M., et al. (2012) · Nature · doi:10.1038/nature11525 · Cited by 359 · see citing works

Three-dimensional culture of melanoma cells profoundly affects gene expression profile: A high density oligonucleotide array study

Ghosh, S., Spagnoli, G. C., Martin, I., Ploegert, S., Demougin, P., Heberer, M., & Reschner, A. (2005) · Journal of Cellular Physiology · doi:10.1002/jcp.20320 · Cited by 326 · see citing works

Human pluripotent stem cell-derived neural constructs for predicting neural toxicity

Schwartz, M. P., Hou, Z., Propson, N. E., Zhang, J., Engstrom, C. J., Costa, V. S., Jiang, P., Nguyen, B. K., Bolin, J. M., Daly, W., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516645112 · Cited by 325 · see citing works

Mesenchymal Stem Cells Support Migration, Extracellular Matrix Invasion, Proliferation, and Survival of Endothelial Cells In Vitro

Potapova, I. A., Gaudette, G. R., Brink, P. R., Robinson, R. B., Rosen, M. R., Cohen, I. S., & Doronin, S. V. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0022 · Cited by 324 · see citing works

Microfluidic Endothelium for Studying the Intravascular Adhesion of Metastatic Breast Cancer Cells

Song, J. W., Cavnar, S. P., Walker, A. C., Luker, K. E., Gupta, M., Tung, Y.-C., Luker, G. D., & Takayama, S. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005756 · Cited by 317 · see citing works

Scaling and systems biology for integrating multiple organs-on-a-chip

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Matched-comparative modeling of normal and diseased human airway responses using a microengineered breathing lung chip

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Tissue Engineering and Developmental Biology: Going Biomimetic

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Distinct types of tumor-initiating cells form human colon cancer tumors and metastases

Dieter, S. M., Ball, C. R., Hoffmann, C. M., Nowrouzi, A., Herbst, F., Zavidij, O., Abel, U., Arens, A., Weichert, W., Brand, K., et al. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.08.010 · Cited by 297 · see citing works

Artificial three-dimensional niches deconstruct pancreas development in vitro

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Multi-parameter phenotypic profiling: using cellular effects to characterize small-molecule compounds

Feng, Y., Mitchison, T. J., Bender, A., Young, D. W., & Tallarico, J. A. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2876 · Cited by 278 · see citing works

Scaffold-free culture of mesenchymal stem cell spheroids in suspension preserves multilineage potential

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3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions

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Compact spheroid formation by ovarian cancer cells is associated with contractile behavior and an invasive phenotype

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