The DOI matches its Crossref record; 42 of the 43 references it cites were found in a registry or an index.
Modelling human development and disease in pluripotent stem-cell-derived gastric organoids
Open accessAbstract
Gastric diseases, including peptic ulcer disease and gastric cancer, affect 10% of the world's population and are largely due to chronic Helicobacter pylori infection. Species differences in embryonic development and architecture of the adult stomach make animal models suboptimal for studying human stomach organogenesis and pathogenesis, and there is no experimental model of normal human gastric mucosa. Here we report the de novo generation of three-dimensional human gastric tissue in vitro through the directed differentiation of human pluripotent stem cells. We show that temporal manipulation of the FGF, WNT, BMP, retinoic acid and EGF signalling pathways and three-dimensional growth are sufficient to generate human gastric organoids (hGOs). Developing hGOs progressed through molecular and morphogenetic stages that were nearly identical to the developing antrum of the mouse stomach. Organoids formed primitive gastric gland- and pit-like domains, proliferative zones containing LGR5-expressing cells, surface and antral mucous cells, and a diversity of gastric endocrine cells. We used hGO cultures to identify novel signalling mechanisms that regulate early endoderm patterning and gastric endocrine cell differentiation upstream of the transcription factor NEUROG3. Using hGOs to model pathogenesis of human disease, we found that H. pylori infection resulted in rapid association of the virulence factor CagA with the c-Met receptor, activation of signalling and induction of epithelial proliferation. Together, these studies describe a new and robust in vitro system for elucidating the mechanisms underlying human stomach development and disease.
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 cited source says what the claim attributes to it.
In the citing paper
“Thus, RA is crucial for human posterior foregut specification, consistent with the role for RA in generating foregut derivatives such as stomach endoderm in vitro (McCracken et al., 2014) and how inhibiting RA synthesis abrogates both liver and pancreas formation in zebrafish embryos (Stafford and Prince, 2002).”
From A Roadmap for Human Liver Differentiation from Pluripotent Stem Cells (2018) · cites this paper as McCracken et al., 2014
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
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,682
Fagerberg, L., Hallström, B. M., Oksvold, P., Kampf, C., Djureinovic, D., Odeberg, J., Habuka, M., Tahmasebpoor, S., Danielsson, A., Edlund, K., et al. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.035600 · Cited by 3,665
Differential analysis of gene regulation at transcript resolution with RNA-seq
Trapnell, C., Hendrickson, D. G., Sauvageau, M., Goff, L., Rinn, J. L., & Pachter, L. (2013) · Nature Biotechnology · doi:10.1038/nbt.2450 · Cited by 3,492
The global health burden of infection‐associated cancers in the year 2002
Parkin, D. M. (2006) · International Journal of Cancer · doi:10.1002/ijc.21731 · Cited by 2,932
Production of pancreatic hormone–expressing endocrine cells from human embryonic stem cells
D’Amour, K. A., Bang, A. G., Eliazer, S., Kelly, O., Agulnick, A. D., Smart, N. G., Moorman, M. A., KROON, E. J., Carpenter, M. K., & Baetge, E. E. (2006) · Nature Biotechnology · doi:10.1038/nbt1259 · Cited by 1,913
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-citationThe NIH Roadmap Epigenomics Mapping Consortium
Bernstein, B. E., Stamatoyannopoulos, J. A., Costello, J. F., Ren, B., Milosavljevic, A., Meissner, A., Kellis, M., Marra, M. A., Beaudet, A. L., Ecker, J. R., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt1010-1045 · Cited by 1,892
Efficient differentiation of human embryonic stem cells to definitive endoderm
D'Amour, K. A., Agulnick, A. D., Eliazer, S., Kelly, O. G., Kroon, E., & Baetge, E. E. (2005) · Nature Biotechnology · doi:10.1038/nbt1163 · Cited by 1,730
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
Cited by
Sorted by citations
Items 301–400 of 990
Generation of Gastrointestinal Organoids from Human Pluripotent Stem Cells
Múnera, J. O., & Wells, J. M. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-6949-4_12 · Cited by 46
Self-citationFagundes, F. L., Pereira, Q. C., Zarricueta, M. L., & dos Santos, R. D. C. (2021) · Nutrients · doi:10.3390/nu13103312 · Cited by 51
“As indicated in the literature, the EGF protein is critical for the proliferation and differentiation of gastric cells, as well as the regulation of glandular morphogenesis in the stomach [48].”
BackgroundLiabeuf, D., Oshima, M., Stange, D. E., & Sigal, M. J. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.12.252 · Cited by 47
Garcia, A. L. C., Arlt, V. M., & Phillips, D. H. (2021) · Mutagenesis · doi:10.1093/mutage/geab023 · Cited by 47
“In a similar way, PSC-derived gut organoids formed simple gland and pit domains and contained Lgr5+ cells as well as mucous and endocrine cells; however, they represented early developmental stages and contained submucosal myofibroblasts and a small population of subepithelial myofibroblasts (32).”
ResultOrganoids as Innovative Models for Bone and Joint Diseases
Huang, J., Zhang, L., Lü, A., & Liang, C. (2023) · Cells · doi:10.3390/cells12121590 · Cited by 48
“For example, the common method used to culture human gastric organoids from PSCs involves the application of a special medium containing the combination of biochemical factors, such as Wnt-3A, FGF4, NOG, epidermal growth factor (EGF), retinoic acid (RA), CHIR99021, and Y-27632, at different stages in a basement matrix…”
MethodRecent 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
Pluripotent stem cell-derived kidney organoids: An in vivo-like in vitro technology
Schutgens, F., Verhaar, M. C., & Rookmaaker, M. B. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.06.059 · Cited by 45
Generation of 3D human gastrointestinal organoids: principle and applications
Zhang, M., Liu, Y., & Chen, Y. (2020) · Cell Regeneration · doi:10.1186/s13619-020-00040-w · Cited by 47
Hein, R. F. C., Conchola, A. S., Fine, A. S., Xiao, Z., Frum, T., Brastrom, L. K., Akinwale, M. A., Childs, C. J., Tsai, Y.-H., Holloway, E. M., et al. (2022) · Development · doi:10.1242/dev.200693 · Cited by 44
Self-citationGastric Organoids: Progress and Remaining Challenges
Pang, M.-J., Burclaff, J., Jin, R. U., Adkins-Threats, M., Osaki, L. H., Han, Y., Mills, J. C., Miao, Z., & Wang, Z.-N. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.09.005 · Cited by 43
Ogaki, S., Morooka, M., Otera, K., & Kume, S. (2015) · Scientific Reports · doi:10.1038/srep17297 · Cited by 43
Adult gastric stem cells and their niches
Bartfeld, S., & Koo, B. (2017) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.261 · Cited by 43
From organoids to organs: Bioengineering liver grafts from hepatic stem cells and matrix
Willemse, J., Lieshout, R., van der Laan, L. J. W., & Verstegen, M. M. A. (2017) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2017.03.003 · Cited by 44
Ernst, K., Schmid, J., Beck, M., Hägele, M., Hohwieler, M., Hauff, P., Ückert, A., Anastasia, A., Fauler, M., Jank, T., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-02882-y · Cited by 43
Modeling rare diseases with induced pluripotent stem cell technology
Anderson, R. H., & Francis, K. R. (2018) · Molecular and Cellular Probes · doi:10.1016/j.mcp.2018.01.001 · Cited by 46
Liu, J., Liu, S., Gao, H., Han, L., Chu, X., Sheng, Y., Wang, Y., Shou, W., Liu, Y., Wan, J., et al. (2020) · Genome biology · doi:10.1186/s13059-020-02082-4 · Cited by 39
Dey, P., & Chaudhuri, S. R. (2022) · Biology · doi:10.3390/biology11050757 · Cited by 45
Designs and methodologies to recreate in vitro human gut microbiota models
Biagini, F., Daddi, C., Calvigioni, M., Maria, C. D., Zhang, Y. S., Ghelardi, E., & Vozzi, G. (2022) · Bio-Design and Manufacturing · doi:10.1007/s42242-022-00210-6 · Cited by 43
3D multicellular systems in disease modelling: From organoids to organ-on-chip
Goldrick, C., Guri, I., Herrera-Oropeza, G. E., O’Brien-Gore, C., Roy, E., Wojtynska, M., & Spagnoli, F. M. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1083175 · Cited by 44
“, 2015), gastric (McCracken et al., 2014), retina (Eiraku et al.”
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
van Loo, B., ten Den, S. A., Araújo‐Gomes, N., de Jong, V., Snabel, R. R., Schot, M., Rivera‐Arbeláez, J. M., Veenstra, G. J. C., Passier, R. C., Kamperman, T., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42297-0 · Cited by 44
Phenotypic Analysis of Organoids by Proteomics
Gonneaud, A., Asselin, C., Boudreau, F., & Boisvert, F. (2017) · PROTEOMICS · doi:10.1002/pmic.201700023 · Cited by 43
“Since then, significant progress has been made in defining optimal conditions to allow growth, expansion and differentiation of stem cells from several different tissues [18-22].”
BackgroundEngineering-derived approaches for iPSC preparation, expansion, differentiation and applications
Li, Y., Li, L., Chen, Z., Gao, G., Yao, R., & Sun, W. (2017) · Biofabrication · doi:10.1088/1758-5090/aa7e9a · Cited by 43
Engineering complexity in human tissue models of cancer
Ronaldson-Bouchard, K., Baldassarri, I., Tavakol, D. N., Graney, P. L., Samaritano, M., Cimetta, E., & Vunjak‐Novakovic, G. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114181 · Cited by 43
Kishimoto, K., Iwasawa, K., Sorel, A., Ferran-Heredia, C., Han, L., Morimoto, M., Wells, J. M., Takebe, T., & Zorn, A. M. (2022) · Nature Protocols · doi:10.1038/s41596-022-00733-3 · Cited by 41
Self-citationHumans in a Dish: The Potential of Organoids in Modeling Immunity and Infectious Diseases
Iakobachvili, N., & Peters, P. J. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.02402 · Cited by 40
“Intestinal (Spence et al., 2011), liver (Takebe et al., 2013), lung (Dye et al., 2015), kidney (Takasato et al., 2015), pancreas (Huang et al., 2015), stomach (McCracken et al., 2014), and retinal (Völkner et al., 2016) organoids can all be cultured from PSC’s.”
BackgroundParihar, A., Pandita, V., & Khan, R. (2022) · Biotechnology and Bioengineering · doi:10.1002/bit.28166 · Cited by 41
“Organoids are extremely impactful for drug screening and customized medicine since they can be extended to offer enough material for investigational testing and are accessible to a broad range of typical experimental lab methods (McCracken et al., 2014).”
BackgroundLooking to the future following 10 years of induced pluripotent stem cell technologies
Li, M., & Belmonte, J. C. I. (2016) · Nature Protocols · doi:10.1038/nprot.2016.108 · Cited by 44
Translational potential of human brain organoids
Sun, A. X., Ng, H., & Tan, E. (2018) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.505 · Cited by 45
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 43
Self-citationPanoutsopoulos, A. A. (2020) · The Neuroscientist · doi:10.1177/1073858420960112 · Cited by 42
Genome engineering of stem cell organoids for disease modeling
Sun, Y., & Ding, Q. (2017) · Protein & Cell · doi:10.1007/s13238-016-0368-0 · Cited by 39
“Current organoids that have been reported to be generated from mouse or human PSCs include stomach (mouse/human) (McCracken et al., 2014; Noguchi et al., 2015), intestine (mouse/human) (McCracken et al., 2011; Ootani et al., 2009; Spence et al., 2011; Watson et al., 2014; Workman et al., 2016),…”
BackgroundTargeting β-cell dedifferentiation and transdifferentiation: opportunities and challenges
Wang, W., & Zhang, C. (2021) · Endocrine Connections · doi:10.1530/ec-21-0260 · Cited by 40
Tissue engineering for the treatment of short bowel syndrome in children
Martin, L. Y., Ladd, M. R., Werts, A. D., Sodhi, C. P., March, J. C., & Hackam, D. J. (2017) · Pediatric Research · doi:10.1038/pr.2017.234 · Cited by 39
The truth aboutin vitroculture ofCryptosporidiumspecies
Karanis, P. (2017) · Parasitology · doi:10.1017/s0031182017001937 · Cited by 39
“Stem cell-derived organoids should recapitulate in vivo physiology of their original tissues, representing valuable systems tomodelmedical disorders such as infectious diseases (McCracken et al. 2014; Ettayebi et al. 2016).”
BackgroundJosenhans, C., Müthing, J., Elling, L., Bartfeld, S., & Schmidt, H. (2020) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2020.151392 · Cited by 40
“Both harbor the specific mucus-producing cells either of the intestine, or the stomach (McCracken et al., 2014; Merrell and Falkow, 2004; Sato et al., 2011, 2009; Spence et al., 2011; Bartfeld et al., 2015).”
Background3D organoids derived from the small intestine: An emerging tool for drug transport research
Zhang, Y., Huang, S., Zhong, W., Chen, W., Yao, B., & Wang, X. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.12.002 · Cited by 40
Enteroendocrine cell differentiation and function in the intestine
Sanchez, J. G., Enriquez, J. R., & Wells, J. M. (2022) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000709 · Cited by 40
Self-citationFrom morphology to single-cell molecules: high-resolution 3D histology in biomedicine
Xu, X., Su, J., Zhu, R., Li, K., Zhao, X., Fan, J., & Mao, F. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02240-x · Cited by 43
Hunsberger, J. G., Efthymiou, A. G., Malik, N., Behl, M., Mead, I., Zeng, X., Simeonov, A. M., & Rao, M. S. (2015) · Stem Cells and Development · doi:10.1089/scd.2014.0531 · Cited by 38
“Another example of developing 3D organoid systems for modeling is demonstrated by developing human gastric organoids (hGOs) [73].”
BackgroundShinozawa, T., Yoshikawa, H., & Takebe, T. (2016) · Developmental Biology · doi:10.1016/j.ydbio.2016.06.036 · Cited by 38
“Therefore, experimental animals transplanted with human iPS cell-derived liver buds and organoids such as the intestine (McCracken et al., 2014; Sinagoga and Wells, 2015)may be used to investigate the mechanism of idiosyncratic DILI in association with another organs.”
BackgroundWang, Y., Takeishi, K., Li, Z., Cervantes‐Alvarez, E., de l’Hortet, A. C., Guzman‐Lepe, J., Cui, X., & Zhu, J. (2017) · Organogenesis · doi:10.1080/15476278.2017.1322243 · Cited by 38
A five-miRNA signature predicts survival in gastric cancer using bioinformatics analysis
Zhang, Z., Dong, Y., Jin, H., Xue, H., Hu, J. M., Jiang, T., Shi, L., & Du, J. (2019) · Gene · doi:10.1016/j.gene.2019.02.058 · Cited by 38
Rallabandi, H. R., Yang, H., Oh, K. B., Lee, H.-C., Byun, S. J., & Lee, B. R. (2020) · Tissue Engineering and Regenerative Medicine · doi:10.1007/s13770-020-00278-0 · Cited by 43
Blake, R. A., Jensen, K., Mabbott, N. A., Hope, J. C., & Stevens, J. M. (2022) · Frontiers in Veterinary Science · doi:10.3389/fvets.2022.921160 · Cited by 38
PFOA and PFOS Disrupt the Generation of Human Pancreatic Progenitor Cells
Liu, S., Yin, N., & Faiola, F. (2018) · Environmental Science & Technology Letters · doi:10.1021/acs.estlett.8b00193 · Cited by 38
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
Gastric epithelial histology and precancerous conditions
Yang, H., Yang, W., & Hu, B. (2022) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v14.i2.396 · Cited by 38
TGF-β Family Signaling in Ductal Differentiation and Branching MorphogenesisPreprint
Kahata, K., Maturi, V., & Moustakas, A. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a031997 · Cited by 38
“Similarly, BMPs in this cocktail induce differentiation of human pluripotent stem cells into three-dimensional mini-stomachs (McCracken et al. 2014).”
BackgroundOrganoids, organs-on-chips and other systems, and microbiota
May, S., Evans, S., & Parry, L. (2017) · Emerging Topics in Life Sciences · doi:10.1042/etls20170047 · Cited by 36
Organoids Provide an Important Window on Inflammation in Cancer
Baker, K. (2018) · Cancers · doi:10.3390/cancers10050151 · Cited by 37
Dzobo, K., Rowe, A., Senthebane, D. A., AlMazyadi, M., Patten, V. A., & Parker, M. I. (2018) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2018.0172 · Cited by 37
“To replicate patho-gens’ entry into cells as seen in vivo , pathogens can be injected into the lumen of formed 3D organoids (McCracken et al., 2014).”
Organoids: Past Learning and Future Directions
O’Connell, L., & Winter, D. C. (2019) · Stem Cells and Development · doi:10.1089/scd.2019.0227 · Cited by 39
Hocevar, S. E., Liu, L., & Duncan, R. K. (2021) · Stem Cell Research · doi:10.1016/j.scr.2021.102295 · Cited by 40
“, 2011), stomach (McCracken et al., 2014), retina (Eiraku et al.”
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
Self-citationThree‐dimensional pancreas organogenesis models
Grapin‐Botton, A. (2016) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12720 · Cited by 41
“ney Diseases (NIDDK) (1U01DK089570-01), as part of the Beta Cell Biology Consortium and grant (12-126875) from Det Frie Forskningsråd/Sundhed og Sygdom.”
BackgroundIşık, M., Okesola, B. O., Eylem, C. C., Koçak, E., Nemutlu, E., D’Este, M., Mata, Á., & Derkuş, B. (2023) · Acta Biomaterialia · doi:10.1016/j.actbio.2023.09.040 · Cited by 36
Modeling Cancer with Pluripotent Stem Cells
Gingold, J. A., Zhou, R., Lemischka, I. R., & Lee, D. (2016) · Trends in cancer · doi:10.1016/j.trecan.2016.07.007 · Cited by 35
“Another protocol for generating PSC-derived gastric organoids [64] was later published by the same group.”
BackgroundVertebrate Axial Patterning: From Egg to Asymmetry
Houston, D. W. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-46095-6_6 · Cited by 36
High-content imaging assays on a miniaturized 3D cell culture platform
Joshi, P., Datar, A., Yu, K., Kang, S., & Lee, M. (2018) · Toxicology in Vitro · doi:10.1016/j.tiv.2018.02.014 · Cited by 36
“The importance of 3D cell culture models in the assessment of mechanisms underlying diseases and mechanisms of action of drugs has been highlighted by several literatures (Booij et al., 2016; Godoy et al., 2013; McCracken et al., 2014; Mueller et al., 2014; Schwartz et al., 2015; Shelper et al., 2016) The ability of 3…”
BackgroundMitotic motor CENP-E cooperates with PRC1 in temporal control of central spindle assembly
Liu, X., Xu, L., Li, J., Yao, P. Y., Wang, W., Ismail, H., Wang, H., Liao, B., Yang, Z., Ward, T. L., et al. (2019) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjz051 · Cited by 34
Zhang, Y., Wu, Y., Wang, J., Hu, Y., Fang, W., Dang, J., Wu, Y., Li, X., Zhao, H., & Li, Z. (2020) · ACS Sustainable Chemistry & Engineering · doi:10.1021/acssuschemeng.0c07209 · Cited by 35
Torrens‐Mas, M., Perelló-Reus, C. M., Navas-Enamorado, C., Ibargüen-González, L., Sánchez-Polo, A., Segura‐Sampedro, J. J., Masmiquel, L., Barceló, C., & González‐Freire, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910547 · Cited by 38
Koide, T., Koyanagi‐Aoi, M., Uehara, K., Kakeji, Y., & Aoi, T. (2022) · iScience · doi:10.1016/j.isci.2022.104314 · Cited by 35
Port d’Entrée for Respiratory Infections – Does the Influenza A Virus Pave the Way for Bacteria?
Siemens, N., Oehmcke-Hecht, S., Mettenleiter, T. C., Kreikemeyer, B., Valentin‐Weigand, P., & Hammerschmidt, S. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.02602 · Cited by 34
“…virus infections of cerebral organoids (Lancaster et al., 2013; Dang et al., 2016), Helicobacter pylori infections of gastric epithelial organoids (McCracken et al., 2014; Schlaermann et al., 2016), Escherichia coli and Rotavirus infections of gastrointestinal and small intestinal enteroids…”
BackgroundSelf-organized formation of developing appendages from murine pluripotent stem cells
Mori, S., Sakakura, E., Tsunekawa, Y., Hagiwara, M., Suzuki, T., & Eiraku, M. (2019) · Nature Communications · doi:10.1038/s41467-019-11702-y · Cited by 35
STAT3: a critical component in the response toHelicobacter pyloriinfection
Menheniott, T. R., Judd, L. M., & Giraud, A. S. (2015) · Cellular Microbiology · doi:10.1111/cmi.12518 · Cited by 34
Human induced pluripotent stem cells: A disruptive innovation
Vos, J. D., Bouckenheimer, J., Sansac, C., Lemaı̂tre, J.-M., & Assou, S. (2016) · Current Research in Translational Medicine · doi:10.1016/j.retram.2016.04.001 · Cited by 37
“001 stomach [53], retinal tissue [54], cerebellum [55] or brain tissue [56].”
BackgroundOrganoids for Advanced Therapeutics and Disease Models
Kim, S., Cho, A., Min, S., Kim, S., & Cho, S. (2018) · Advanced Therapeutics · doi:10.1002/adtp.201800087 · Cited by 33
Engineering tissue‐specific blood vessels
Herron, L. A., Hansen, C. S., & Abaci, H. E. (2019) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10139 · Cited by 32
Gastrointestinal organoids: a next-generation tool for modeling human development
Singh, A., Poling, H. M., Spence, J. R., Wells, J. M., & Helmrath, M. A. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00199.2020 · Cited by 33
Self-citationThree-Dimensional Culture Systems in Gastric Cancer Research
Alzeeb, G., Metges, J., Corcos, L., & Jossic-Corcos, C. L. (2020) · Cancers · doi:10.3390/cancers12102800 · Cited by 38
Tissue Engineering for Musculoskeletal Regeneration and Disease Modeling
Li, Z. A., Xiang, S., Li, E. N., Fritch, M. R., Alexander, P. G., Lin, H., & Tuan, R. S. (2020) · Handbook of experimental pharmacology · doi:10.1007/164_2020_377 · Cited by 34
Organoids in modelling infectious diseases
Shpichka, A. I., Bikmulina, P., Peshkova, M., Heydari, Z., Kosheleva, N. V., Vosough, M., & Timashev, P. S. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.08.005 · Cited by 35
Translational models of 3-D organoids and cancer stem cells in gastric cancer research
Wuputra, K., Ku, C., Kato, K., Wu, D., Saito, S., & Yokoyama, K. K. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02521-4 · Cited by 33
“D) endoderm into 3D-gut spheroids are performed by the activation of Wnt and FGF4 [6].”
BackgroundInfluentialChen, J., Lau, B. T., Andor, N., Grimes, S. M., Handy, C., Wood-Bouwens, C. M., & Ji, H. P. (2019) · Scientific Reports · doi:10.1038/s41598-019-40809-x · Cited by 37
Insights on Three Dimensional Organoid Studies for Stem Cell Therapy in Regenerative Medicine
Mulaudzi, P. E., Abrahamse, H., & Crous, A. (2023) · Stem Cell Reviews and Reports · doi:10.1007/s12015-023-10655-6 · Cited by 38
Human stem cell-based disease modeling: prospects and challenges
Johnson, J. Z., & Hockemeyer, D. F. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2015.10.007 · Cited by 33
“Organoid systems have so far been established to model a variety of organs such as the intestine [46 ], stomach [47,48], pancreas [49], mammary tissue [50], brain [51], liver [52], and lung [53].”
BackgroundDesign 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
From Definitive Endoderm to Gut—a Process of Growth and Maturation
Guiu, J., & Jensen, K. B. (2015) · Stem Cells and Development · doi:10.1089/scd.2015.0017 · Cited by 32
“Exciting recent developments have revealed that the gut epithelium derived from pluripotent stem cells, when transplanted with nonepithelial cells, transits from an immature to an adult epithelium, thereby recapitulating the behavior of fetal-derived intestinal epithelium [97,122,123].”
A decade of liver organoids: Advances in disease modeling
Liu, Y., Sheng, J.-Y., Yang, C.-F., Ding, J., & Chan, Y.-S. (2023) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2022.0428 · Cited by 30
Mammalian tracheal development and reconstruction: insights from in vivo and in vitro studies
Kishimoto, K., & Morimoto, M. (2021) · Development · doi:10.1242/dev.198192 · Cited by 33
Translating Developmental Principles to Generate Human Gastric Organoids
Eicher, A. K., Berns, H. M., & Wells, J. M. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.12.014 · Cited by 34
Self-citationBailey, D. D., Zhang, Y., van Soldt, B. J., Jiang, M. Z., Suresh, S., Nakagawa, H., Rustgi, A. K., Aceves, S. S., Cardoso, W. V., & Que, J. (2019) · Development · doi:10.1242/dev.178855 · Cited by 31
Liu, C., Niu, K., & Xiao, Q. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa313 · Cited by 31
Lizarraga, S. B., Ma, L., Maguire, A. M., van Dyck, L. I., Wu, Q., Ouyang, Q., Kavanaugh, B. C., Nagda, D., Livi, L. L., Pescosolido, M. F., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.aaw0682 · Cited by 33
Development of an automated 3D high content cell screening platform for organoid phenotyping
Bozal, S. B., Sjogren, G., Costa, A. P., Brown, J. S., Roberts, S., Baker, D. S., Gabriel, P., Ristau, B. T., Samuels, M. L., Flynn, W. F., et al. (2024) · SLAS DISCOVERY · doi:10.1016/j.slasd.2024.100182 · Cited by 35
“…standardizing the starting size of organoids, each with tradeoffs, that have been implemented across various starting cell types including adult stem cells (ASCs) as either tissue fragments or single cell suspensions [21-23], pluripotent stem cells (PSCs) [24-26], or fetal progenitor cells [27,28].”
Lane, A. N., Higashi, R. M., & Fan, T. W. ‐. (2016) · Metabolomics · doi:10.1007/s11306-016-1065-y · Cited by 32
“It is also possible to generate spheroids or whole organoids containing multiple cell types (Lee et al. 2007; Willyard 2015; McCracken et al. 2014; Spence et al. 2011), which much more closely mimic the natural tissue, while retaining the flexibility for experimental manipulation in much the same…”
BackgroundSelf-organization in development, regeneration and organoids
Werner, S., Vu, H. T.-K., & Rink, J. C. (2016) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2016.09.002 · Cited by 32
Chen, Z., Kheiri, S., Gevorkian, A., Young, E. W. K., Andre, V., Deisenroth, T. W., & Kumacheva, E. (2021) · Lab on a Chip · doi:10.1039/d1lc00619c · Cited by 30
Induced Pluripotent Stem Cells
Fakoya, A. O. J., Omole, A. E., Satyadev, N., & Haider, K. H. (2022) · Springer eBooks · doi:10.1007/978-981-16-6016-0_40-1 · Cited by 29
Organoids as preclinical models of human disease: progress and applications
Chen, B., Du, C., Wang, M., Guo, J., & Liu, X. (2024) · Medical Review · doi:10.1515/mr-2023-0047 · Cited by 31
“Matrigel, an EHS mouse sarcoma extract [17], contains laminin and a number of growth factors, which are extensively used in organoid cultures, such as gastric [18], mammary glands [19], intestinal [11], and brain [20].”
BackgroundKan, L., Yu, Y., Wang, Y., Shi, L., Fan, T., Chen, H., & Ren, C. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02328-4 · Cited by 32
Ogoke, O., Maloy, M. H., & Parashurama, N. (2020) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12650 · Cited by 28
“Since embryogenesis and organogenesis involve spatial cellular communication and tissue dynamics (Lancaster et al., 2013; McCracken et al., 2014; Rios & Clevers, 2018), and organoids can recapitulate these processes, non-invasive imaging of intact organoids can provide insights into morphogenesis…”
BackgroundSelf-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 33
“the body axis—a concept that was further exploited to produce colonic organoids [77], stomach antrum-like organoids [38], and lung organoids [10, 78].”
BackgroundOncogenic potential of human pluripotent stem cell‐derived lung organoids with HER2 overexpression
Miura, A., Yamada, D., Nakamura, M., Tomida, S., Shimizu, D., Jiang, Y., Takao, T., Yamamoto, H., Suzawa, K., Shien, K., et al. (2021) · International Journal of Cancer · doi:10.1002/ijc.33713 · Cited by 29
In Vitro Model of Human Trophoblast in Early Placentation
Bačenková, D., Trebuňová, M., Čı́žková, D., Hudák, R., Dosedla, E., Balogová, A. F., & Živčák, J. (2022) · Biomedicines · doi:10.3390/biomedicines10040904 · Cited by 32
“Significant progress has been made in designing various protocols for human organoids, such as the brain [8,9], lungs [10], liver [11], kidneys [12,13], prostate [14], retina [15] and gastrointestinal tissues [16,17].”
Background3D Human Organoids: The Next “Viral” Model for the Molecular Basis of Infectious Diseases
Chia, S. P. S., Kong, S. L. Y., Pang, J. K. S., & Soh, B.-S. (2022) · Biomedicines · doi:10.3390/biomedicines10071541 · Cited by 28
Organ regeneration based on developmental biology: past and future
Takeo, M., & Tsuji, T. (2018) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2018.05.008 · Cited by 31
Farzaneh, Z., Najarasl, M., Abbasalizadeh, S., Vosough, M., & Baharvand, H. (2018) · Stem Cells and Development · doi:10.1089/scd.2017.0074 · Cited by 28
“Since insulin protects cell viability and vitamin A acts as a posteriorizing factor [34], we have used the B-27 supplement with insulin and without vitamin A in our study.”
Metadata
- Authors
- 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., & Wells, J. M.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- University of Cincinnati (US)
- University of Michigan (US)
- Corresponding author
- Zavros, Yana
- Wells, James M.
- ORCID
- Venue
- Nature
- Published
- 2014-10-29
- Volume
- 516
- Issue
- 7531
- Pages
- 400-404
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4270898
- OpenAlex
- W2054186703
- Cited by
- 980
- References
- 43
- Citations by year
- 2026: 54 · 2025: 67 · 2024: 87 · 2023: 69 · 2022: 104 · 2021: 106 · 2020: 96 · 2019: 79 · 2018: 82 · 2017: 93 · 2016: 86 · 2015: 50 · 2014: 6
- FWCI
- 32.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (5ul1rr026314-03)
- National Institute of General Medical Sciences (T32GM063483, R01GM072915)
- National Institute of Allergy and Infectious Diseases (U19AI116491)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK034933, K01DK091415, P30 DK0789392, R01DK083402, R01DK098350, R01DK080823, R01DK092456, P30DK078392)
- National Center for Research Resources (UL1-RR026314, U54-RR-025216)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Gastroenterology › Helicobacter pylori-related gastroenterology studies
- Keywords
- gastric organoids, human pluripotent stem cells, induced pluripotent stem cells, human embryonic stem cells, gastric epithelium, Helicobacter pylori infection, CagA, c-Met, gastric endocrine cells, Lgr5, Neurog3, signaling pathways, peptic ulcer, gastric cancer, in vitro disease model
- MeSH terms
- Cell Differentiation, Humans, Models, Biological, Organoids, Stomach, Signal Transduction, Helicobacter pylori, Helicobacter Infections, Organogenesis, Pluripotent Stem Cells
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
