Nonadhesive Alginate Hydrogels Support Growth of Pluripotent Stem Cell-Derived Intestinal Organoids
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Abstract
Human intestinal organoids (HIOs) represent a powerful system to study human development and are promising candidates for clinical translation as drug-screening tools or engineered tissue. Experimental control and clinical use of HIOs is limited by growth in expensive and poorly defined tumor-cell-derived extracellular matrices, prompting investigation of synthetic ECM-mimetics for HIO culture. Since HIOs possess an inner epithelium and outer mesenchyme, we hypothesized that adhesive cues provided by the matrix may be dispensable for HIO culture. Here, we demonstrate that alginate, a minimally supportive hydrogel with no inherent cell instructive properties, supports HIO growth in vitro and leads to HIO epithelial differentiation that is virtually indistinguishable from Matrigel-grown HIOs. In addition, alginate-grown HIOs mature to a similar degree as Matrigel-grown HIOs when transplanted in vivo, both resembling human fetal intestine. This work demonstrates that purely mechanical support from a simple-to-use and inexpensive hydrogel is sufficient to promote HIO survival and development.
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Mechanical properties of the cell and tissue microenvironment play an important role in cell survival, proliferation, migration, and tissue differentiation.
“Mechanical properties, e.g., ECM stiffness, of the cell and tissue microenvironment are known to play an important role in cell survival [53,54], proliferation[55], migration[56], and tissue differentiation[57,58].”
Organoid types grown in alginate include human lung, human brain, murine intestinal, human intestinal, human pancreatic, and human and murine vascular.
“Organoid types grown in alginate include human lung99,100, human brain101, murine intestinal102, human intestinal102,103, human pancreatic104, and human and murine vascular105.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [103]
Several laboratories have grown a wide range of organoids in polysaccharides such as alginate or alginate-chitosan mixtures.
“In addition to organoids grown in naturally-derived proteins, several laboratories have grown a wide range of organoids in polysaccharides such as alginate or alginate-chitosan mixtures.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [103]
Differentiation of human pluripotent cells into human intestinal organoids could be supported on an alginate substrate without the alginate providing chemical cues to the cells.
“Capeling and colleagues grew HIOs on an alginate substrate and found that differentiation of human pluripotent cells into HIOs could be supported without the alginate providing chemical cues to the cells.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [103]
There have been a number of studies showing that organoids can be grown on unmodified surfaces such as alginate, but this requires more research.
“There have been a number of studies showing that organoids can be grown on unmodified surfaces such as alginate, but this requires more research103,105,110,175,183.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [103]
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Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
Near-optimal probabilistic RNA-seq quantification
Bray, N. L., Pimentel, H., Melsted, P., & Pachter, L. (2016) · Nature Biotechnology · doi:10.1038/nbt.3519 · Cited by 9,723 · see citing works
Alginate: Properties and biomedical applications
Lee, K. Y., & Mooney, D. J. (2011) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2011.06.003 · Cited by 8,218 · see citing works
Cerebral organoids model human brain development and microcephaly
Lancaster, M. A., Renner, M., Martin, C.-A., Wenzel, D., Bicknell, L. S., Hurles, M. E., Homfray, T., Penninger, J. M., Jackson, A. P., & Knoblich, J. A. (2013) · Nature · doi:10.1038/nature12517 · Cited by 5,372 · see citing works
Alginate hydrogels as synthetic extracellular matrix materials
Rowley, J. A., Madlambayan, G., & Mooney, D. J. (1999) · Biomaterials · doi:10.1016/s0142-9612(98)00107-0 · Cited by 2,342 · see citing works
Vascularized and functional human liver from an iPSC-derived organ bud transplant
Takebe, T., Sekine, K., Enomura, M., Koike, H., Kimura, M., Ogaeri, T., Zhang, R.-R., Ueno, Y., Zheng, Y.-W., Koike, N., et al. (2013) · Nature · doi:10.1038/nature12271 · Cited by 2,170 · see citing works
Self-organizing optic-cup morphogenesis in three-dimensional culture
Eiraku, M., Takata, N., Ishibashi, H., Kawada, M., Sakakura, E., Okuda, S., Sekiguchi, K., Adachi, T., & Sasai, Y. (2011) · Nature · doi:10.1038/nature09941 · Cited by 2,001 · see citing works
Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro
Spence, J. R., Mayhew, C. N., Rankin, S. A., Kuhar, M. F., Vallance, J. E., Tolle, K. A., Hoskins, E. E., Kalinichenko, V. V., Wells, S. I., Zorn, A. M., et al. (2010) · Nature · doi:10.1038/nature09691 · Cited by 1,911 · see citing works
Self-citationAlginate Hydrogels as Biomaterials
Augst, A., Kong, H. J., & Mooney, D. J. (2006) · Macromolecular Bioscience · doi:10.1002/mabi.200600069 · Cited by 1,849 · see citing works
Designer matrices for intestinal stem cell and organoid culture
Gjorevski, N., Sachs, N., Manfrin, A., Giger, S., Bragina, M. E., Ordóñez-Morán, P., Clevers, H., & Lutolf, M. P. (2016) · Nature · doi:10.1038/nature20168 · Cited by 1,426 · see citing works
Modelling human development and disease in pluripotent stem-cell-derived gastric organoids
McCracken, K. W., Catá, E. M., Crawford, C. M., Sinagoga, K. L., Schumacher, M., Rockich, B. E., Tsai, Y.-H., Mayhew, C. N., Spence, J. R., Zavros, Y., et al. (2014) · Nature · doi:10.1038/nature13863 · Cited by 980 · see citing works
Self-citationIn vitro generation of human pluripotent stem cell derived lung organoids
Dye, B. R., Hill, D. R., Ferguson, M. A. H., Tsai, Y.-H., Nagy, M. S., Dyal, R., Wells, J. M., Mayhew, C. N., Nattiv, R., Klein, O. D., et al. (2015) · eLife · doi:10.7554/elife.05098 · Cited by 824 · see citing works
Self-citationTakasato, M., Er, P. X., Becroft, M., Vanslambrouck, J. M., Stanley, E. G., Elefanty, A. G., & Little, M. H. (2013) · Nature Cell Biology · doi:10.1038/ncb2894 · Cited by 723 · see citing works
An in vivo model of human small intestine using pluripotent stem cells
Watson, C. L., Mahé, M. M., Múnera, J. O., Howell, J. C., Sundaram, N., Poling, H. M., Schweitzer, J. I., Vallance, J. E., Mayhew, C. N., Sun, Y., et al. (2014) · Nature Medicine · doi:10.1038/nm.3737 · Cited by 561 · see citing works
Self-citationSynthetic hydrogels for human intestinal organoid generation and colonic wound repair
Cruz-Acuña, R., Quirós, M., Farkas, A. E., Dedhia, P. H., Huang, S., Siuda, D., García-Hernández, V., Miller, A. J., Spence, J. R., Nusrat, A., et al. (2017) · Nature Cell Biology · doi:10.1038/ncb3632 · Cited by 558 · see citing works
Self-citationViscoelastic Properties of Living Embryonic Tissues: a Quantitative Study
Forgács, G., Foty, R. A., Shafrir, Y., & Steinberg, M. S. (1998) · Biophysical Journal · doi:10.1016/s0006-3495(98)77932-9 · Cited by 485 · see citing works
Generating human intestinal tissue from pluripotent stem cells in vitro
McCracken, K. W., Howell, J. C., Wells, J. M., & Spence, J. R. (2011) · Nature Protocols · doi:10.1038/nprot.2011.410 · Cited by 433 · see citing works
Self-citationThe hope and the hype of organoid research
Huch, M., Knoblich, J. A., Lutolf, M. P., & Martinez-Arias, A. (2017) · Development · doi:10.1242/dev.150201 · Cited by 409 · cited 1× · see citing works
“A pivotal development in the fields of developmental biology and regenerative medicine was the use of human pluripotent stem cells (hPSCs) to generate human cell types, tissues, and organoid model systems in vitro (Huch et al., 2017; Johnston, 2015; Little, 2017).”
MethodViscoelastic hydrogels for 3D cell culture
Chaudhuri, O. (2017) · Biomaterials Science · doi:10.1039/c7bm00261k · Cited by 353 · see citing works
Leslie, J. L., Huang, S., Opp, J. S., Nagy, M. S., Kobayashi, M., Young, V. B., & Spence, J. R. (2014) · Infection and Immunity · doi:10.1128/iai.02561-14 · Cited by 330 · see citing works
Self-citationSox17 Regulates Organ Lineage Segregation of Ventral Foregut Progenitor Cells
Spence, J. R., Lange, A. W., Lin, S. J., Kaestner, K. H., Lowy, A. M., Kim, I., Whitsett, J. A., & Wells, J. M. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.05.012 · Cited by 302 · see citing works
Self-citationSelf-organization of a human organizer by combined Wnt and Nodal signalling
Martyn, I., Kanno, T. Y. N., Ruzo, A., Siggia, E. D., & Brivanlou, A. H. (2018) · Nature · doi:10.1038/s41586-018-0150-y · Cited by 301 · see citing works
Heijmans, J., van Lidth de Jeude, J. F., Koo, B.-K., Rosekrans, S. L., Wielenga, M. C. B., van de Wetering, M., Ferrante, M., Lee, A. S., Onderwater, J. J. M., Paton, J. C., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.02.031 · Cited by 293 · see citing works
Múnera, J. O., Sundaram, N., Rankin, S. A., Hill, D. R., Watson, C. L., Mahé, M. M., Vallance, J. E., Shroyer, N. F., Sinagoga, K. L., Zarzoso-Lacoste, A., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.05.020 · Cited by 252 · see citing works
Self-citationFinkbeiner, S. R., Hill, D. R., Altheim, C. H., Dedhia, P. H., Taylor, M. J., Tsai, Y.-H., Chin, A. M., Mahé, M. M., Watson, C. L., Freeman, J. J., et al. (2015) · Stem Cell Reports · doi:10.1016/j.stemcr.2015.04.010 · Cited by 250 · see citing works
Self-citationOrganoid Models of Human Gastrointestinal Development and Disease
Dedhia, P. H., Bertaux‐Skeirik, N., Zavros, Y. L., & Spence, J. R. (2016) · Gastroenterology · doi:10.1053/j.gastro.2015.12.042 · Cited by 246 · see citing works
Self-citationMiller, A. J., Hill, D. R., Nagy, M. S., Aoki, Y., Dye, B. R., Chin, A. M., Huang, S., Zhu, F., White, E. S., Lama, V. N., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.11.012 · Cited by 235 · see citing works
Self-citationDye, B. R., Dedhia, P. H., Miller, A. J., Nagy, M. S., White, E. S., Shea, L. D., & Spence, J. R. (2016) · eLife · doi:10.7554/elife.19732 · Cited by 191 · see citing works
Self-citationR-spondin 2 is required for normal laryngeal-tracheal, lung and limb morphogenesis
Bell, S. M., Schreiner, C. M., Wert, S. E., Mucenski, M. L., Scott, W. J., & Whitsett, J. A. (2008) · Development · doi:10.1242/dev.013359 · Cited by 191 · see citing works
Wells, J. M., & Spence, J. R. (2014) · Development · doi:10.1242/dev.097386 · Cited by 174 · see citing works
Self-citationFinkbeiner, S. R., Freeman, J. J., Wieck, M. M., El-Nachef, W., Altheim, C. H., Tsai, Y.-H., Huang, S., Dyal, R., White, E. S., Grikscheit, T. C., et al. (2015) · Biology Open · doi:10.1242/bio.013235 · Cited by 174 · see citing works
Self-citationHill, D. R., Huang, S., Nagy, M. S., Yadagiri, V. K., Fields, C., Thornhill, D., Bons, B., Dedhia, P. H., Chin, A. M., Tsai, Y.-H., et al. (2017) · eLife · doi:10.7554/elife.29132 · Cited by 173 · see citing works
Self-citationPEG-4MAL hydrogels for human organoid generation, culture, and in vivo delivery
Cruz-Acuña, R., Quirós, M., Huang, S., Siuda, D., Spence, J. R., Nusrat, A., & García, A. J. (2018) · Nature Protocols · doi:10.1038/s41596-018-0036-3 · Cited by 168 · see citing works
Self-citationEnemchukwu, N. O., Cruz‐Acuña, R., Bongiorno, T., Johnson, C. T., García, J. R., Sulchek, T., & Garcı́a, A. J. (2015) · The Journal of Cell Biology · doi:10.1083/jcb.201506055 · Cited by 125 · see citing works
Strain Dependence of the Viscoelastic Properties of Alginate Hydrogels
Webber, R. E., & Shull, K. R. (2004) · Macromolecules · doi:10.1021/ma049274n · Cited by 114 · see citing works
Biochemical and Physical Signal Gradients in Hydrogels to Control Stem Cell Behavior
Jeon, O., Alt, D. S., Linderman, S. W., & Alsberg, E. (2013) · Advanced Materials · doi:10.1002/adma.201302364 · Cited by 101 · see citing works
Self-citationGenerating human intestinal tissues from pluripotent stem cells to study development and disease
Sinagoga, K. L., & Wells, J. M. (2015) · The EMBO Journal · doi:10.15252/embj.201490686 · Cited by 93 · see citing works
Tsai, Y.-H., Nattiv, R., Dedhia, P. H., Nagy, M. S., Chin, A. M., Thomson, M., Klein, O. D., & Spence, J. R. (2016) · Development · doi:10.1242/dev.138453 · Cited by 87 · see citing works
Self-citationSamorezov, J. E., Morlock, C. M., & Alsberg, E. (2015) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.5b00117 · Cited by 86 · see citing works
Self-citationA Method for Cryogenic Preservation of Human Biopsy Specimens and Subsequent Organoid Culture
Tsai, Y.-H., Czerwinski, M. J., Wu, A., Dame, M. K., Attili, D., Hill, E. M., Colacino, J. A., Nowacki, L. M., Shroyer, N. F., Higgins, P., et al. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.04.008 · Cited by 80 · see citing works
Self-citationhPSC-derived lung and intestinal organoids as models of human fetal tissue
Aurora, M., & Spence, J. R. (2016) · Developmental Biology · doi:10.1016/j.ydbio.2016.06.006 · Cited by 69 · see citing works
Self-citationIdentification, isolation and characterization of human LGR5-positive colon adenoma cells
Dame, M. K., Attili, D., McClintock, S. D., Dedhia, P. H., Ouillette, P. D., Hardt, O., Chin, A. M., Xue, X., Laliberté, J., Katz, E. L., et al. (2018) · Development · doi:10.1242/dev.153049 · Cited by 68 · see citing works
Self-citationRheological Evaluation of Inter-grade and Inter-batch Variability of Sodium Alginate
Fu, S., Thacker, A., Sperger, D. M., Boni, R. L., Velankar, S., Munson, E. J., & Block, L. H. (2010) · AAPS PharmSciTech · doi:10.1208/s12249-010-9547-0 · Cited by 67 · see citing works
A process engineering approach to increase organoid yield
Arora, N., Alsous, J. I., Guggenheim, J. W., Mak, M., Múnera, J. O., Wells, J. M., Kamm, R. D., Asada, H. H., Shvartsman, S. Y., & Griffith, L. G. (2017) · Development · doi:10.1242/dev.142919 · Cited by 62 · see citing works
A molecular scheme for improved characterization of human embryonic stem cell lines
Josephson, R., Sykes, G., Liu, Y., Ording, C., Xu, W., Zeng, X., Shin, S., Loring, J. F., Maitra, A., Rao, M. S., et al. (2006) · BMC Biology · doi:10.1186/1741-7007-4-28 · Cited by 52 · see citing works
Matsuo, Y., Nishizaki, C., & Drexler, H. G. (1999) · PubMed · Cited by 31 · see citing works
The Renaissance of Developmental Biology
Johnston, D. S. (2015) · PLoS Biology · doi:10.1371/journal.pbio.1002149 · Cited by 29 · see citing works
LGR4 and LGR5 Function Redundantly During Human Endoderm Differentiation
Tsai, Y.-H., Hill, D. R., Kumar, N., Huang, S., Chin, A. M., Dye, B. R., Nagy, M. S., Verzi, M. P., & Spence, J. R. (2016) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2016.06.002 · Cited by 27 · see citing works
Self-citationCzerwinski, M. J., & Spence, J. R. (2017) · Cell stem cell · doi:10.1016/j.stem.2016.12.010 · Cited by 27 · see citing works
Self-citationLittle, M. H. (2017) · Development · doi:10.1242/dev.150292 · Cited by 17 · see citing works
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Alginate: From Food Industry to Biomedical Applications and Management of Metabolic Disorders
Gheorghita, R. E., Lobiuc, A., Dimian, M., & Covașă, M. (2020) · Polymers · doi:10.3390/polym12102417 · Cited by 473 · see citing works
Next-generation cancer organoids
LeSavage, B. L., Suhar, R. A., Broguière, N., Lütolf, M. P., & Heilshorn, S. C. (2021) · Nature Materials · doi:10.1038/s41563-021-01057-5 · Cited by 462 · see citing works
Engineered materials for organoid systems
Kratochvil, M. J., Seymour, A. J., Li, T. L., Pașca, S. P., Kuo, C. J., & Heilshorn, S. C. (2019) · Nature Reviews Materials · doi:10.1038/s41578-019-0129-9 · Cited by 413 · see citing works
Towards organoid culture without Matrigel
Kozlowski, M. T., Crook, C. J., & Ku, H. T. (2021) · Communications Biology · doi:10.1038/s42003-021-02910-8 · Cited by 409 · see citing works
Engineering Stem Cell Self-organization to Build Better Organoids
Brassard, J. A., & Lütolf, M. P. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.05.005 · Cited by 379 · see citing works
Kim, S., Min, S., Choi, Y. S., Jo, S.-H., Jung, J. H., Han, K., Kim, J., An, S., Ji, Y. W., Kim, Y.-G., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29279-4 · Cited by 375 · see citing works
Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip
Liu, H., Wang, Y., Cui, K., Guo, Y., Zhang, X., & Qin, J. (2019) · Advanced Materials · doi:10.1002/adma.201902042 · Cited by 353 · see citing works
Bioengineering Approaches for the Advanced Organoid Research
Yi, S. A., Zhang, Y., Rathnam, C., Pongkulapa, T., & Lee, K. (2021) · Advanced Materials · doi:10.1002/adma.202007949 · Cited by 218 · see citing works
Thorel, L., Perréard, M., Florent, R., Divoux, J., Coffy, S., Vincent, A., Gaggioli, C., Guasch, G., Gidrol, X., Weiswald, L., et al. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01272-5 · Cited by 228 · see citing works
Kim, W., Gwon, Y., Park, S., Kim, H., & Kim, J. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.03.039 · Cited by 211 · see citing works
AI-enabled organoids: Construction, analysis, and application
Bai, L., Wu, Y., Li, G., Zhang, W., Zhang, H., & Su, J. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.09.005 · Cited by 216 · see citing works
Mapping Development of the Human Intestinal Niche at Single-Cell Resolution
Holloway, E. M., Czerwinski, M. J., Tsai, Y.-H., Wu, J. H., Wu, A., Childs, C. J., Walton, K. D., Sweet, C. W., Yu, Q., Glass, I. A., et al. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.11.008 · Cited by 171 · see citing works
Self-citationHernandez‐Gordillo, V., Kassis, T., Lampejo, A. O., Choi, G., Gamboa, M. E., Gnecco, J. S., Brown, A., Breault, D. T., Carrier, R. L., & Griffith, L. G. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2020.120125 · Cited by 177 · see citing works
Charting human development using a multi-endodermal organ atlas and organoid models
Yu, Q., Kilik, U., Holloway, E. M., Tsai, Y.-H., Harmel, C., Wu, A., Wu, J. H., Czerwinski, M. J., Childs, C. J., He, Z., et al. (2021) · Cell · doi:10.1016/j.cell.2021.04.028 · Cited by 145 · see citing works
Self-citationNon-matrigel scaffolds for organoid cultures
Kaur, S., Kaur, I., Rawal, P., Tripathi, D. M., & Vasudevan, A. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.01.025 · Cited by 150 · see citing works
Organoids in gastrointestinal diseases: From experimental models to clinical translation
Günther, C., Winner, B., Neurath, M. F., & Stappenbeck, T. S. (2022) · Gut · doi:10.1136/gutjnl-2021-326560 · Cited by 145 · see citing works
Indana, D., Agarwal, P., Bhutani, N., & Chaudhuri, O. (2021) · Advanced Materials · doi:10.1002/adma.202101966 · Cited by 139 · see citing works
Human organoids-on-chips for biomedical research and applications
Wang, H., Ning, X., Zhao, F. H., Zhao, H., & Li, D. (2024) · Theranostics · doi:10.7150/thno.90492 · Cited by 138 · see citing works
Differentiation of Human Intestinal Organoids with Endogenous Vascular Endothelial Cells
Holloway, E. M., Wu, J. H., Czerwinski, M. J., Sweet, C. W., Wu, A., Tsai, Y.-H., Huang, S., Stoddard, A. E., Capeling, M. M., Glass, I. A., et al. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.07.023 · Cited by 125 · see citing works
Self-citationResearch Progress, Challenges, and Breakthroughs of Organoids as Disease Models
Huang, Y., Huang, Z., Tang, Z., Chen, Y., Huang, M., Liu, H., Huang, W., Ye, Q., & Jia, B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.740574 · Cited by 128 · see citing works
Advances in Spheroids and Organoids on a Chip
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Recent advances in defined hydrogels in organoid research
Gan, Z., Qin, X., Liu, H., Liu, J., & Qin, J. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.06.004 · Cited by 127 · see citing works
Engineering the Extracellular Matrix for Organoid Culture
Heo, J. H., Kang, D., Seo, S. J., & Jin, Y. (2022) · International Journal of Stem Cells · doi:10.15283/ijsc21190 · Cited by 116 · see citing works
Gnecco, J. S., Brown, A., Buttrey, K., Ives, C., Goods, B. A., Baugh, L. M., Hernandez‐Gordillo, V., Loring, M., Isaacson, K., & Griffith, L. G. (2023) · Med · doi:10.1016/j.medj.2023.07.004 · Cited by 122 · see citing works
Generation of mesenchyme free intestinal organoids from human induced pluripotent stem cells
Mithal, A., Capilla, A., Heinze, D. M., Berical, A. C., Villacorta-Martín, C., Vedaie, M., Jacob, A., Abo, K. M., Szymaniak, A. D., Peasley, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13916-6 · Cited by 111 · see citing works
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Ruiter, F. A. A., Morgan, F. L. C., Roumans, N. J. T., Schumacher, A., Slaats, G. G. G., Moroni, L., LaPointe, V. L. S., & Baker, M. B. (2022) · Advanced Science · doi:10.1002/advs.202200543 · Cited by 92 · see citing works
Organ-on-Chip Approaches for Intestinal 3D In Vitro Modeling
Pimenta, J. M., Ribeiro, R. D. C., Almeida, R., Costa, P. F., da Silva, M. A., & Pereira, B. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.08.015 · Cited by 92 · see citing works
Fang, G., Lu, H., de la Fuente, L. R., Law, A. M. K., Lin, G., Jin, D., & Gallego‐Ortega, D. (2021) · Advanced Science · doi:10.1002/advs.202102418 · Cited by 91 · see citing works
Microphysiological Systems: Design, Fabrication, and Applications
Wang, K., Man, K., Liu, J., Liu, Y., Chen, Q., Zhou, Y., & Yang, Y. S. (2020) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.9b01667 · Cited by 83 · see citing works
Complex in vitro model: A transformative model in drug development and precision medicine
Wang, L., Hu, D., Xu, J., Hu, J., & Wang, Y. (2023) · Clinical and Translational Science · doi:10.1111/cts.13695 · Cited by 87 · see citing works
Standardization of organoid culture in cancer research
Zhou, C., Wu, Y., Wang, Z., Liu, Y., Yu, J., Wang, W., Chen, S., Wu, W., Wang, J., Qian, G., et al. (2023) · Cancer Medicine · doi:10.1002/cam4.5943 · Cited by 84 · see citing works
One-step synthesis of composite hydrogel capsules to support liver organoid generation from hiPSCs
Wang, Y., Liu, H., Zhang, M., Wang, H., Chen, W., & Qin, J. (2020) · Biomaterials Science · doi:10.1039/d0bm01085e · Cited by 78 · see citing works
Stem Cell Signaling Pathways in the Small Intestine
Takahashi, T., & Shiraishi, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21062032 · Cited by 75 · see citing works
Long-term flow through human intestinal organoids with the gut organoid flow chip (GOFlowChip)
Sidar, B., Jenkins, B. R., Huang, S., Spence, J. R., Walk, S. T., & Wilking, J. N. (2019) · Lab on a Chip · doi:10.1039/c9lc00653b · Cited by 74 · see citing works
Self-citationHydrogels for Large-Scale Expansion of Stem Cells
Yin, S., & Cao, Y. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.03.026 · Cited by 73 · see citing works
A thermo-responsive collagen-nanocellulose hydrogel for the growth of intestinal organoids
Curvello, R., Alves, D., Abud, H. E., & Garnier, G. (2021) · Materials Science and Engineering C · doi:10.1016/j.msec.2021.112051 · Cited by 74 · see citing works
Engineered Plant‐Based Nanocellulose Hydrogel for Small Intestinal Organoid Growth
Curvello, R., Kerr, G., Micati, D., Chan, W. H., Raghuwanshi, V. S., Rosenbluh, J., Abud, H. E., & Garnier, G. (2020) · Advanced Science · doi:10.1002/advs.202002135 · Cited by 72 · see citing works
Biomaterial-guided stem cell organoid engineering for modeling development and diseases
Hoang, P., & Ma, Z. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.01.026 · Cited by 70 · see citing works
Standardization and consensus in the development and application of bone organoids
Jian, W., Chen, X., Li, R., Wang, S., Geng, Z., Shi, Z., Jing, Y., Xu, K., Wei, Y., Wang, G., et al. (2024) · Theranostics · doi:10.7150/thno.105840 · Cited by 72 · see citing works
Geuens, T., Ruiter, F. A. A., Schumacher, A., Morgan, F. L. C., Rademakers, T., Wiersma, L. E., van den Berg, C. W., Rabelink, T. J., Baker, M. B., & LaPointe, V. L. S. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120976 · Cited by 67 · see citing works
Microstructured Hydrogels to Guide Self‐Assembly and Function of Lung Alveolospheres
Loebel, C., Weiner, A. I., Eiken, M. K., Katzen, J. B., Morley, M. P., Bala, V., Cardenas‐Diaz, F. L., Davidson, M. D., Shiraishi, K., Basil, M. C., et al. (2022) · Advanced Materials · doi:10.1002/adma.202202992 · Cited by 64 · see citing works
Self-citationKim, S., Byun, H., Lee, S., Kim, E., Lee, G. M., Huh, S. J., Joo, J., & Shin, H. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.01.047 · Cited by 64 · see citing works
Chooi, W. H., Ng, C. Y., Ow, V., Harley, J., Ng, W., Hor, J., Low, K. E., Malleret, B., Xue, K., & Ng, S. (2022) · Advanced Healthcare Materials · doi:10.1002/adhm.202202342 · Cited by 62 · see citing works
Repair and regeneration of small intestine: A review of current engineering approaches
Qi, D., Shi, W., Black, A. R., Kuss, M. A., Pang, X., He, Y., Liu, B., & Duan, B. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.119832 · Cited by 59 · see citing works
Advancing Tissue Decellularized Hydrogels for Engineering Human Organoids
Moura, B. S., Monteiro, M. V., Ferreira, L. P., Lavrador, P., Gaspar, V. M., & Mano, J. F. (2022) · Advanced Functional Materials · doi:10.1002/adfm.202202825 · Cited by 63 · see citing works
Reproducible extracellular matrices for tumor organoid culture: challenges and opportunities
Li, K., He, Y., Jin, X., Jin, K., & Qian, J. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06349-x · Cited by 68 · see citing works
Advanced lung organoids for respiratory system and pulmonary disease modeling
Joo, H., Min, S., & Cho, S. (2024) · Journal of Tissue Engineering · doi:10.1177/20417314241232502 · Cited by 60 · see citing works
Liu, Y., Huang, J., Li, S., Li, Z., Chen, C., Qu, G., Chen, K., Teng, Y., Ma, R., Wu, X., et al. (2023) · Biomaterials Science · doi:10.1039/d3bm01645e · Cited by 59 · see citing works
Hydrogel Mechanics Influence the Growth and Development of Embedded Brain Organoids
Cassel de Camps, C., Aslani, S., Stylianesis, N., Nami, H., Mohamed, N.-V., Durcan, T. M., & Moraes, C. (2022) · ACS Applied Bio Materials · doi:10.1021/acsabm.1c01047 · Cited by 55 · see citing works
Engineered organoids for biomedical applications
de Barros, N. R., Wang, C., Maity, S., Peirsman, A., Nasiri, R., Herland, A., Ermis, M., Kawakita, S., de Carvalho, B. G., Kouchehbaghi, N. H., et al. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.115142 · Cited by 56 · see citing works
Self-citationMultifunctional alginate/polydeoxyribonucleotide hydrogels for promoting diabetic wound healing
Dananjaya, S. H. S., Bandara, N., Molagoda, I. M. N., Sandamalika, W. M. G., Kim, D., Ganepola, N., Attanayake, A. P., & Choi, D. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.128367 · Cited by 52 · see citing works
Song, Y., Uchida, H., Sharipol, A., Piraino, L. R., Mereness, J. A., Ingalls, M. H., Rebhahn, J. A., Newlands, S. D., DeLouise, L. A., Ovitt, C. E., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-01876-x · Cited by 51 · see citing works
Self-citationHierarchical assembly of tryptophan zipper peptides into stress-relaxing bioactive hydrogels
Nguyen, A. K., Molley, T. G., Kardia, E., Ganda, S., Chakraborty, S., Wong, S. L., Ruan, J., Yee, B. E., Mata, J. P., Vijayan, A., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41907-1 · Cited by 50 · see citing works
Engineering the 3D structure of organoids
Moss, S. P., Bakırcı, E., & Feinberg, A. W. (2024) · Stem Cell Reports · doi:10.1016/j.stemcr.2024.11.009 · Cited by 51 · see citing works
A bioengineering perspective on modelling the intestinal epithelial physiology in vitro
Antfolk, M., & Jensen, K. B. (2020) · Nature Communications · doi:10.1038/s41467-020-20052-z · Cited by 52 · see citing works
Advanced biomedical applications based on emerging 3D cell culturing platforms
Wang, A., Madden, L. A., & Paunov, V. N. (2020) · Journal of Materials Chemistry B · doi:10.1039/d0tb01658f · Cited by 49 · see citing works
In Vitro Models of the Small Intestine: Engineering Challenges and Engineering Solutions
Hewes, S. A., Wilson, R. L., Estes, M. K., Shroyer, N. F., Blutt, S. E., & Grande-Allen, K. J. (2020) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2019.0334 · Cited by 47 · see citing works
Wallaschek, N., Niklas, C., Pompaiah, M., Wiegering, A., Germer, C., Kircher, S., Brändlein, S., Maurus, K., Rosenwald, A., Yan, H. H. N., et al. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.05.031 · Cited by 45 · see citing works
Treacy, N. J., Clerkin, S., Davis, J. L., Kennedy, C., Miller, A. F., Saiani, A., Wychowaniec, J. K., Brougham, D. F., & Crean, J. K. G. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.08.003 · Cited by 46 · see citing works
Engineered biomimetic hydrogels for organoids
Li, Y., Saiding, Q., Wang, Z., & Cui, W. (2023) · Progress in Materials Science · doi:10.1016/j.pmatsci.2023.101216 · Cited by 45 · see citing works
Synthetic Matrices for Intestinal Organoid Culture: Implications for Better Performance
Poudel, H., Sanford, K., Szwedo, P. K., Pathak, R., & Ghosh, A. (2021) · ACS Omega · doi:10.1021/acsomega.1c05136 · Cited by 45 · see citing works
Recent advances in organoid engineering: A comprehensive review
Unagolla, J. M., & Jayasuriya, A. C. (2022) · Applied Materials Today · doi:10.1016/j.apmt.2022.101582 · Cited by 44 · see citing works
Intestinal Stem Cell-on-Chip to Study Human Host-Microbiota Interaction
Siwczak, F., Loffet, E. A., Kaminska, M., Koceva, H., Mahé, M. M., & Mosig, A. S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.798552 · Cited by 44 · see citing works
A Sustainable Solution to Skin Diseases: Ecofriendly Transdermal Patches
Yilmaz, E. G., Ece, E., Erdem, Ö., Eş, İ., & İnci, F. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020579 · Cited by 42 · see citing works
Takahashi, Y., Inoue, Y., Sato, S., Okabe, T., Kojima, H., Kiyono, H., Shimizu, M., Yamauchi, Y., & Sato, R. (2023) · Scientific Reports · doi:10.1038/s41598-023-32438-2 · Cited by 41 · see citing works
Composition and Mechanism of Three-Dimensional Hydrogel System in Regulating Stem Cell Fate
Ma, J., & Huang, C. (2020) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2020.0021 · Cited by 42 · see citing works
Recent advances in chemically defined and tunable hydrogel platforms for organoid culture
Agarwal, T., Celikkin, N., Costantini, M., Maiti, T. K., & Makvandi, P. (2021) · Bio-Design and Manufacturing · doi:10.1007/s42242-021-00126-7 · Cited by 42 · see citing works
Biomaterials for intestinal organoid technology and personalized disease modeling
Hirota, A., AlMusawi, S., Nateri, A. S., Ordóñez‐Morán, P., & Imajo, M. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.05.010 · Cited by 41 · see citing works
Exploiting CRISPR Cas9 in Three-Dimensional Stem Cell Cultures to Model Disease
Gopal, S., Rodrigues, A. L., & Dordick, J. S. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00692 · Cited by 44 · see citing works
Bioactive peptides for boosting stem cell culture platform: Methods and applications
Dayem, A. A., Lee, S. B., Lim, K. M., Kim, A., Shin, H. J., Vellingiri, B., Kim, Y. B., & Cho, S. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114376 · Cited by 41 · see citing works
hPSC-derived organoids: models of human development and disease
Frum, T., & Spence, J. R. (2020) · Journal of Molecular Medicine · doi:10.1007/s00109-020-01969-w · Cited by 40 · see citing works
Self-citationEngineered Synthetic Matrices for Human Intestinal Organoid Culture and Therapeutic Delivery
Mulero‐Russe, A., & Garcı́a, A. J. (2023) · Advanced Materials · doi:10.1002/adma.202307678 · Cited by 40 · see citing works
Ma, P., Chen, Y., Lai, X., Zheng, J., Ye, E., Loh, X. J., Zhao, Y., Parikh, B. H., Su, X., You, M., et al. (2021) · Macromolecular Bioscience · doi:10.1002/mabi.202100191 · Cited by 39 · see citing works
Liu, Y., Dabrowska, C., Mavousian, A., Strauss, B., Meng, F., Mazzaglia, C., Ouaras, K., Macintosh, C., Terentjev, E. M., Lee, J., et al. (2021) · Advanced Science · doi:10.1002/advs.202003332 · Cited by 36 · see citing works
Suspension culture promotes serosal mesothelial development in human intestinal organoids
Capeling, M. M., Huang, S., Childs, C. J., Wu, J. H., Tsai, Y.-H., Wu, A., Garg, N., Holloway, E. M., Sundaram, N., Bouffi, C., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110379 · Cited by 36 · see citing works
Self-citationAdvances of Engineered Hydrogel Organoids within the Stem Cell Field: A Systematic Review
Li, Z., Yue, M., Liu, Y., Zhang, P., Qing, J., Liu, H., & Zhou, Y. (2022) · Gels · doi:10.3390/gels8060379 · Cited by 35 · see citing works
A fully defined 3D matrix for ex vivo expansion of human colonic organoids from biopsy tissue
Bergenheim, F. H., Fregni, G., Buchanan, C. F., Riis, L. B., Heulot, M., Touati, J., Seidelin, J. B., Rizzi, S. C., & Nielsen, O. H. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120248 · Cited by 33 · see citing works
Curvello, R., & Garnier, G. (2020) · Biomacromolecules · doi:10.1021/acs.biomac.0c01510 · Cited by 34 · see citing works
Liver organoid culture methods
Hu, Y., Hu, X., Luo, J. C., Huang, J., Sun, Y., Li, H., Qiao, Y., Wu, H., Li, J., Zhou, L., et al. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01136-x · Cited by 33 · see citing works
Design Approaches for Generating Organ Constructs
Xia, Y. F., & Belmonte, J. C. I. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.05.016 · Cited by 32 · see citing works
Kim, S., Choi, Y. S., Lee, J. S., Jo, S.-H., Kim, Y., & Cho, S. (2021) · Journal of Industrial and Engineering Chemistry · doi:10.1016/j.jiec.2021.11.044 · Cited by 32 · see citing works
Advances in biomimetic hydrogels for organoid culture
Luo, L., Liu, L., Ding, Y., Dong, Y., & Ma, M. (2023) · Chemical Communications · doi:10.1039/d3cc01274c · Cited by 35 · see citing works
Ort, C., Chen, Y., Ghagre, A., Ehrlicher, A. J., & Moraes, C. (2021) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.1c00129 · Cited by 31 · see citing works
Engineered biomaterials in stem cell-based regenerative medicine
Zhu, F., Nie, G., & Liu, C. (2023) · Life Medicine · doi:10.1093/lifemedi/lnad027 · Cited by 32 · see citing works
Alginate-based bioink for organoid 3D bioprinting: A review
Leonardo, M., Prajatelistia, E., & Judawisastra, H. (2022) · Bioprinting · doi:10.1016/j.bprint.2022.e00246 · Cited by 31 · see citing works
Xu, Z. Z., Huang, J., Liu, Y., Chen, C., Qu, G., Wang, G., Zhao, Y., Wu, X., & Ren, J. (2022) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10327 · Cited by 31 · see citing works
Toward reproducible tumor organoid culture: focusing on primary liver cancer
Guo, L., Li, C., & Gong, W. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1290504 · Cited by 32 · see citing works
Self-organization of organoids from endoderm-derived cells
Lewis, A. C., Keshara, R., Kim, Y. H., & Grapin‐Botton, A. (2020) · Journal of Molecular Medicine · doi:10.1007/s00109-020-02010-w · Cited by 30 · see citing works
Emerging role and promise of nanomaterials in organoid research
Mahapatra, C., Lee, A., & Paul, M. K. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.11.007 · Cited by 31 · see citing works
Hydrogels: A potential platform for induced pluripotent stem cell culture and differentiation
Poorna, M. R., Jayakumar, R., Chen, J., & Mony, U. (2021) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2021.111991 · Cited by 28 · see citing works
Challenges to, and prospects for, reverse engineering the gastrointestinal tract using organoids
Kakni, P., Truckenmüller, R. K., Habibović, P., & Giselbrecht, S. (2022) · Trends in biotechnology · doi:10.1016/j.tibtech.2022.01.006 · Cited by 28 · see citing works
Alginate microfibers as therapeutic delivery scaffolds and tissue mimics
Xie, Y., Kollampally, S. C. R., Jorgensen, M., & Zhang, X. (2022) · Experimental Biology and Medicine · doi:10.1177/15353702221112905 · Cited by 28 · see citing works
Silk fibroin-alginate based beads for human mesenchymal stem cell differentiation in 3D
Patil, S., & Singh, N. (2019) · Biomaterials Science · doi:10.1039/c9bm01000a · Cited by 28 · see citing works
- Authors
- Capeling, M. M., Czerwinski, M., Huang, S., Tsai, Y.-H., Wu, A., Nagy, M. S., Juliar, B., Sundaram, N., Song, Y., Han, W. M., Takayama, S., Alsberg, E., Garcia, A. J., Helmrath, M., Putnam, A. J., & Spence, J. R.
- Affiliations
- University of Michigan (US)
- Cincinnati Children's Hospital Medical Center (US)
- Georgia Institute of Technology (US)
- Case Western Reserve University (US)
- Corresponding author
- Spence, Jason R.
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 12
- Issue
- 2
- Pages
- 381-394
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC6373433
- OpenAlex
- W2949559557
- Cited by
- 226
- References
- 50
- Citations by year
- 2026: 11 · 2025: 39 · 2024: 19 · 2023: 30 · 2022: 35 · 2021: 45 · 2020: 33 · 2019: 14
- FWCI
- 10.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Intestinal Stem Cell Consortium (U01DK103141)
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Allergy and Infectious Diseases
- Novel Alternative Model Systems for Enteric Diseases (U19AI116482)
- Cellular and Biotechnology Training Program (T32GM008353)
- Training Program in Organogenesis Fellowship (T32HD007505)
- NICHD (R24HD000836)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- human intestinal organoids, alginate hydrogel, extracellular matrix mimics, pluripotent stem cells, organoid transplantation, mechanical support, organoid maturation
- MeSH terms
- Alginates, Animals, Cell Differentiation, Cell Line, Collagen, Drug Combinations, Epithelium, Extracellular Matrix, Humans, Intestines, Laminin, Organoids, Proteoglycans, Mice, SCID, Mice, Inbred NOD, Hydrogels, Tissue Engineering, Pluripotent Stem Cells, Mice
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