The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Synthetic hydrogels for human intestinal organoid generation and colonic wound repair
Open accessAbstract
In vitro differentiation of human intestinal organoids (HIOs) from pluripotent stem cells is an unparalleled system for creating complex, multicellular three-dimensional structures capable of giving rise to tissue analogous to native human tissue. Current methods for generating HIOs rely on growth in an undefined tumour-derived extracellular matrix (ECM), which severely limits the use of organoid technologies for regenerative and translational medicine. Here, we developed a fully defined, synthetic hydrogel based on a four-armed, maleimide-terminated poly(ethylene glycol) macromer that supports robust and highly reproducible in vitro growth and expansion of HIOs, such that three-dimensional structures are never embedded in tumour-derived ECM. We also demonstrate that the hydrogel serves as an injection vehicle that can be delivered into injured intestinal mucosa resulting in HIO engraftment and improved colonic wound repair. Together, these studies show proof-of-concept that HIOs may be used therapeutically to treat intestinal injury.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Matrigel is mainly comprised of laminin, collagen IV, entactin, perlecan and growth factors, and is similar in composition to the basement membrane62.”
From Organoids (2022) · cites this paper as [62]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Therefore, other matrices with defined compositions64 have been explored as alternative matrices to Matrigel, such as recombinant human collagen62, fibrin65, or synthetic hydrogels3,63.”
From Organoids (2022) · cites this paper as [62]
In the citing paper
“These spheroids are being used to emulate organs such as the intestine2, liver3, kidney4, brain5, and heart6 to study human development and disease in vitro.”
From 3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels (2021) · cites this paper as [2]
In the citing paper
“Organoid viability was reduced at high PEG density and matrix stiffness;”
From Towards organoid culture without Matrigel (2021) · cites this paper as [163]
In the citing paper
“Intriguingly, when PEG was crosslinked with dithiothreitol to inhibit matrix degradation, organoid viability at seven days was poor as measured by live-dead staining.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [163]
In the citing paper
“Cruz-Acuna and colleagues also found that PEG-based materials may need to be soft and degradable in order to support differentiated intestinal organoids.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [163]
In the citing paper
“RGD- or AG73 (CGGRKRLQVQLSIRT)-functionalized PEG matrices promoted greater organoid viability than laminin-derived IKVAV- or type I collagen-derived GFOGER peptides163,164.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [163]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221
Embryonic Stem Cell Lines Derived from Human Blastocysts
Thomson, J. A., Itskovitz‐Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., & Jones, J. M. (1998) · Science · doi:10.1126/science.282.5391.1145 · Cited by 15,947
Identification of stem cells in small intestine and colon by marker gene Lgr5
Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., et al. (2007) · Nature · doi:10.1038/nature06196 · Cited by 5,687
Modeling Development and Disease with Organoids
Clevers, H. (2016) · Cell · doi:10.1016/j.cell.2016.05.082 · Cited by 3,196
Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension
Uehata, M., Ishizaki, T., Satoh, H., Ono, T., Kawahara, T., Morishita, T., Tamakawa, H., Yamagami, K., Inui, J., Maekawa, M., et al. (1997) · Nature · doi:10.1038/40187 · Cited by 2,862
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
Self-citationLong-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver
Huch, M., Gehart, H., van Boxtel, R., Hamer, K., Blokzijl, F., Verstegen, M. M. A., Ellis, E., van Wenum, M., Fuchs, S. A., de Ligt, J., et al. (2015) · Cell · doi:10.1016/j.cell.2014.11.050 · Cited by 1,619
Matrigel: A complex protein mixture required for optimal growth of cell culture
Hughes, C. S., Postovit, L. M., & Lajoie, G. A. (2010) · PROTEOMICS · doi:10.1002/pmic.200900758 · Cited by 1,534
Organoids as an in vitro model of human development and disease
Fatehullah, A., Tan, S. H., & Barker, N. (2016) · Nature Cell Biology · doi:10.1038/ncb3312 · Cited by 1,508
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
Dissecting temporal and spatial control of cytokinesis with a myosin II Inhibitor
Straight, A. F., Cheung, A., Limouze, J., Chen, I., Westwood, N. J., Sellers, J. R., & Mitchison, T. J. (2003) · Science · doi:10.1126/science.1081412 · Cited by 1,412
The promise of induced pluripotent stem cells in research and therapy
Robinton, D. A., & Daley, G. Q. (2012) · Nature · doi:10.1038/nature10761 · Cited by 1,150
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
In 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 846
Self-citationFunctional 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
van der Flier, L. G., Haegebarth, A., Stange, D. E., van de Wetering, M., & Clevers, H. C. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.05.035 · Cited by 581
Dekkers, J. F., Berkers, G., Kruisselbrink, E., Vonk, A., de Jonge, H. R., Janssens, H. M., Bronsveld, I., van de Graaf, E. A., Nieuwenhuis, E. E. S., Houwen, R. H. J., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad8278 · Cited by 548
Phelps, E. A., Enemchukwu, N. O., Fiore, V. F., Sy, J. C., Murthy, N., Sulchek, T., Barker, T. H., & Garcı́a, A. J. (2011) · Advanced Materials · doi:10.1002/adma.201103574 · Cited by 541
Self-citationGenerating 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
Self-citationLeoni, G., Neumann, P., Kamaly, N., Quirós, M., Nishio, H., Jones, H. R., Sumagin, R., Hilgarth, R., Alam, A. M., Fredman, G., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci76693 · Cited by 362
Self-citationLeslie, 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
Self-citationUse of differentiated pluripotent stem cells in replacement therapy for treating disease
Fox, I. J., Daley, G. Q., Goldman, S. A., Huard, J., Kamp, T. J., & Trucco, M. (2014) · Science · doi:10.1126/science.1247391 · Cited by 295
Defined three-dimensional microenvironments boost induction of pluripotency
Caiazzo, M., Okawa, Y., Ranga, A., Piersigilli, A., Tabata, Y., & Lutolf, M. P. (2016) · Nature Materials · doi:10.1038/nmat4536 · Cited by 271
Finkbeiner, 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 260
Self-citationKita‐Matsuo, H., Barcová, M., Prigozhina, N. L., Salomonis, N., Wei, K. A., Jacot, J. G., Nelson, B., Spiering, S., Haverslag, R. T., Kim, C., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005046 · Cited by 227
Dye, 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 197
Self-citationHoffman, M. P., Nomizu, M., Roque, E., Lee, S. C. L., Jung, D. W., Yamada, Y., & Kleinman, H. K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.44.28633 · Cited by 187
Gerbe, F., Brulin, B., Makrini, L., Legraverend, C., & Jay, P. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.06.072 · Cited by 177
Wells, J. M., & Spence, J. R. (2014) · Development · doi:10.1242/dev.097386 · Cited by 174
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
Self-citationPhelps, E. A., Headen, D. M., Taylor, W. R., Thulé, P. M., & Garcı́a, A. J. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.03.012 · Cited by 170
Self-citationStructure of the Integrin α2β1-binding Collagen Peptide
Emsley, J., Knight, C. G., Farndale, R. W., & Barnes, M. J. (2003) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.11.030 · Cited by 135
Besson, D., Pavageau, A.-H., Valo, I., Bourreau, A., Bélanger, A., Eymerit-Morin, C., Moulière, A., Chassevent, A., Boisdron-Celle, M., Morel, A., et al. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.009712 · Cited by 133
Laminin-111-derived peptides and cancer
Kikkawa, Y., Hozumi, K., Katagiri, F., Nomizu, M., Kleinman, H. K., & Koblinski, J. E. (2013) · Cell Adhesion & Migration · doi:10.4161/cam.22827 · Cited by 132
Enemchukwu, 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
Self-citationA developmental framework for induced pluripotency
Takahashi, K., & Yamanaka, S. (2015) · Development · doi:10.1242/dev.114249 · Cited by 114
Genetic Analyses of Integrin SignalingPreprint
Wickstrom, S. A., Radovanac, K., & Fassler, R. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005116 · Cited by 95
Distribution of intestinal stem cell markers in colorectal precancerous lesions
Jang, B. G., Kim, H. S., Kim, K. J., Rhee, Y.-Y., Kim, W. H., & Kang, G. H. (2015) · Histopathology · doi:10.1111/his.12787 · Cited by 38
Cited by
Sorted by citations
Effects of extracellular matrix viscoelasticity on cellular behaviour
Chaudhuri, O., Cooper-White, J., Janmey, P. A., Mooney, D. J., & Shenoy, V. B. (2020) · Nature · doi:10.1038/s41586-020-2612-2 · Cited by 2,224
Progress and potential in organoid research
Rossi, G., Manfrin, A., & Lutolf, M. P. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0051-9 · Cited by 1,182
Hofer, M., & Lutolf, M. P. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00279-y · Cited by 1,184
Synthetic alternatives to Matrigel
Aisenbrey, E. A., & Murphy, W. L. (2020) · Nature Reviews Materials · doi:10.1038/s41578-020-0199-8 · Cited by 1,016
Tales from the crypt: new insights into intestinal stem cells
Gehart, H., & Clevers, H. C. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0081-y · Cited by 1,046
Metadata
- Authors
- 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., & García, A. J.
- Affiliations
- University of Michigan (US)
- HUN-REN Szegedi Biológiai Kutatóközpont (HU)
- Corresponding author
- Spence, Jason R.
- Nusrat, Asma
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2017-10-23
- Volume
- 19
- Issue
- 11
- Pages
- 1326-1335
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC5664213
- OpenAlex
- W2766832099
- Cited by
- 558
- References
- 38
- Citations by year
- 2026: 47 · 2025: 72 · 2024: 42 · 2023: 64 · 2022: 71 · 2021: 99 · 2020: 76 · 2019: 51 · 2018: 32 · 2017: 3
- FWCI
- 17.06
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Georgia Institute of Technology
- University of Georgia
- Crohn's and Colitis Foundation (326912)
- National Institutes of Health (UL1TR000454)
- National Heart, Lung, and Blood Institute (R01HL119215, R21HL115372)
- National Institute of General Medical Sciences (T32GM007315)
- National Institute of Allergy and Infectious Diseases (U19AI116482)
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK085532, R01DK055679, R56DK089763, R29DK055679, R01DK059888, U01DK085532, U01DK103141, R01DK089763)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR062368, R01AR062920)
- National Institute of Dental and Craniofacial Research (T32DE007057)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007505)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- synthetic hydrogels, human intestinal organoids, pluripotent stem cells, organoid expansion, intestinal mucosal injury, regenerative medicine
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Colon, Extracellular Matrix, Humans, Intestinal Mucosa, Intestines, Organoids, Regeneration, Wound Healing, Hydrogels, Pluripotent Stem Cells, Mice
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
