Literature sources included in this study were retrieved from the WoSCC database. The database was searched by combining the terms “organoid”, “gastroid”, “spheroid”, “gastric”, “gastritis”, and “stomach”. Studies published from 2010 up to September 2023 were searched to form the basis of data processing and analysis.

Data extracted from the studies retrieved in the literature search of the WoSCC database included author information, title, keywords, abstract, and references, and underwent preliminary screening. Quantitative variables were analyzed using spreadsheet software (Excel 2019, Microsoft Corporation, Redmond, WA, United States). Citespace version 6.1.R3, developed by Chen Chaomei, and VOSviewer version 1.68, developed by Nees Jan van Eck and Ludo Waltman, were used for scientific knowledge mapping and analysis[13,14]. VOSviewer 1.68 was used to calculate citations and publications of authors and institutions, and to depict the keyword network graph[15,16]. Citespace 6.1.R3 was used to calculate co-cite and citation frequencies, centrality, keyword bursts, references, as well as to depict a network graph of authors, institutions, and a timeline graph of keywords[17].

Citation analysis is a statistical method of illustrating the quantity of cited studies to identify patterns and measurement characteristics. Generally, the more often a study is cited, the greater its impact. Co-citation is when 2 studies are cited by ≥ 1 study at the same time, which indicates how closely the 2 studies are related[18,19]. Moreover, the greater the number of studies cited simultaneously, the closer the relationship between the two. Centrality is an indicator of the importance of a node in a network, and documents with high centrality are often the key hubs connecting two different domains. Evolution of a field of knowledge can be indicated by references with citation bursts. A burst is a keyword/citation reference that has received scholarly attention in a particular field. The timeline is presented as a blue bar, while the interval, when a topic is found to have a burst, is presented as a red section indicating the year it started, the year it ended, and the time of the burst. Higher intensity indicates a higher citation frequency.

Each circle on the network map represents an “individual”, and the size of the circle represents the active degree and the number of publications of the keyword. The closer the distance between an “individual” and an “individual”, the closer the relationship between them. The increased number of connected lines indicates the increased number of co-citations between the “individual”[14].

A total of 656 articles were retrieved in the literature search. The successful culture of gastric-like organs was first reported in 2010, and relevant research developed slowly and steadily in the ensuing years[8]. The number of publications and citations exhibited stable growth from 2010 to 2016 and then a sharp increase after 2017 (Figure 1A). Researchers discovered the great advantage of the organoid model in the past 5 years; therefore, relevant publications and citations have increased rapidly. Most articles have been high quality and were published in Gastroenterology, International Journal of Molecular Science, Cancers, Cellular and Molecular Gastroenterology and Hepatology, Nature Communications, Cancer Research, Cancer Science, and Gut (Figure 1B). These journals focus mainly on cancer and gastroenterological diseases.

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Figure 1 Publication and citation trends in gastric organoid. A: The number of publications and citations per year from 2010 to 2023. The red bars represent the number of publications, and the green line indicates the number of citations, showing an overall upward trend in both metrics over the given period; B: Citations in different medical journals in a recent year, with each color-coded section corresponding to a different journal. The size of each section reflects the number of citations, and the number is provided within each, with Gastroenterology and Cancers being among the journals with the highest citation counts.

A total of 474 investigators published research in this area, with 32 publishing > 5 studies. Yana Zavros, Hans Clevers, James M Wells, Sato Toshiro, and Koo Bon-kyoung were the 5 most productive authors. Hans Clevers, Huch Meritxell, Johan H van Es, Marc Van de Wetering, and Sato Toshiro were the 5 most popular scientists. Hans Clevers, Yana Zavros, and Richard Peek demonstrated high centrality (0.04). Most of the productive and influential investigators were from The Netherlands and the United States, mainly from the University Medical Center Utrecht (Utrecht, Netherlands) and the University of Cincinnati (Cincinnati, OH, United States), respectively. Table 1 summarizes the top 15 most cited researchers and their respective countries.

Hans Clevers, Sato Toshiro, Sina Bartfeld, N Barker, Huch Meritxel, and Marc van de Wetering established a close and vital cooperative network. HHN Yang worked closely with T Seldlitz, G Vlachogiannis worked closely with L Broutier, and another network was formed between S Takaishi and A Jemal. The co-authorship network diagram is presented in Figure 2A.

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Figure 2 Network analysis of key scholars and institutions in gastric organoid research (2010-2023). A: Depicts the collaboration and citation network among key scholars in the field, where the size of the nodes represents the citation count, and the color gradient indicates the year of publication (from light for 2010 to dark for 2023); B: The network positioning and relationships of major research institutions, with node size and color coding similarly representing the volume of citations and the temporal progression of research.

A total of 314 institutions published research on this topic, and 54 published > 5 studies. The top 5 most-productive institutions in this context were the University of Cincinnati, Hiroshima University, University of Michigan (Ann Arbor, MI, United States), Vanderbilt University (Nashville, TN, United States), and the University Medical Center Utrecht. The top 5 most cited institutions were the University Medical Center Utrecht, the Netherlands Institute for Developmental Biology Utrecht, University of Cincinnati, University of Hong Kong, and the University of Michigan. The top 15 most-cited institutions, which were mostly from the Netherlands, United States, China, and Japan, are summarized in Table 2. The University of Cincinnati had the highest centrality (0.25), followed by the University Medical Center Utrecht (0.18).

The United States had the most extensive cooperative network. The University of Cincinnati, Vanderbilt University, University of Michigan, and Cincinnati Children’s Hospital Medicine Center formed the centers of each United States-collaborating institution. Chinese and Japanese scientists contributed the most to research from Asian institutions. Nanjing University (Nanjing, Jiangsu Province, China), Sun Yat-sen University (Guangzhou, Guangdong Province, China), and Fudan University (Shanghai, China) played central roles in the Chinese institutional network of collaborations, radiating out to other institutions. Japanese institutions were dominated, in this context, by Hiroshima University (Hiroshima, Japan), with more collaborations with the University of Cincinnati and other Japanese and Korean institutions.

The University Medical Center Utrecht in the Netherlands has a network of collaborations with European institutions. A network diagram illustrating institutional collaboration is presented in Figure 2B.

VOSviewer was used to construct a keyword network graph. Based on the network analysis the high-frequency keywords of published articles were clustered into 4 categories. The orange area (cluster #1, “Gastric organoid formation”) included the main terms related to gastric organoid construction such as stem cells, gastric epithelium, pyloric gland, and fundic gland. The green area (cluster #2, “Gastric cancer organoid formation”) explored gastric organoid construction such as tumor stem cells, tumor proliferation and differentiation, and immunohistochemistry. The blue area (cluster #3, “Applications of gastric cancer organoids”) occupied a large panel and described the application of organoids in GC therapeutic research, which indicated the study of tumor drug resistance, gene mutations, signaling pathways, and immunohistochemistry. It contains proteins such as WNT, kif11, and pi3k. Another interesting finding in these network diagrams is the red cluster, which is related to the application of organoids in gastritis (cluster #4, “Application of organoid in gastritis research”), including Helicobacter pylori (H. pylori) infection, inflammatory pathway activation, and cagA proteins (Figure 3). Many early studies investigating organoids focused on the formation and differentiation of GC organoids, whereas more recent studies focused on the treatment and mechanism of gastritis and GC.

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Figure 3 Keyword co-occurrence network in gastric organoid research. This visualization maps the interconnectivity of keywords within the gastric organoid literature, with node size indicating the frequency of keyword occurrence and edge thickness representing the strength of the keyword co-occurrence.

After filtering out non-relevant and repetitive keywords, such as “expression” and “identification”, the 20 most popular keywords in the field of gastric organoids were shortlisted and are summarized in Table 3. GC and H. pylori-related gastritis were identified as the most prevalent diseases. Stem cells, cancer stem cells, epithelial cells, progenitor cells, and chief cells were identified as the main cellular “hotpot”. Cellular events related to cancer development and progression, such as metastasis, proliferation, apoptosis, migration, epithelial-mesenchymal transition, and mutation have received more attention.

In addition, burst keywords were considered to be the indicators of emerging trends. Overall, it can be classified into 3 phases, beginning from 2010 to 2014 with high intensity in drug resistance, cancer stem cell, and self-renewal, followed by that from 2015 to 2020 with epithelium, carcinoma, epithelial-mesenchymal transition, H. pylori, inflammation, and regeneration year by year, and the third phase from 2020 until present with mutation, response, tumor microenvironment, and paclitaxel. Figure 4 depicts the keywords with the strongest citation bursts in this field.

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Figure 4 Top 20 keywords with the strongest citation bursts. The bar chart highlights keywords that have experienced significant surges in citations over specific time periods, with the length and color of the bars indicating the duration and intensity of the citation bursts, respectively.

The timeline view of the keywords in gastric organoid is presented in Figure 5. There were a total of 17 main research clusters incorporating gastric organoid applications. In addition, the typical labels in each cluster are reported in Table 4.

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Figure 5 Timeline visualization of thematic evolution in gastric organoid research. This timeline graphically represents the evolution of research themes in the field of gastric organoids, with cluster size indicating the number of publications and connecting lines representing thematic shifts over time.

A total of 492 references were co-cited, 11 of which were co-cited > 30 times. Table 5 summarizes the top 10 co-cited studies, and Figure 6 illustrates the main elements of these important studies investigating gastric organoids and the significant findings. McCracken et al[20] used human pluripotent stem cells to form gastric organoids by adding essential cellular factors [such as EGF, BMP4, WNT5a, and fibroblast growth factors (e.g., FGF10)]. Bartfeld et al[6] used flow cytometry to sort 4 specific cell lines, pit mucous cells, gland mucous cells, chief cells, and enteroendocrine cells, and successfully cultured the corresponding organoid lines. Schlaermann et al[7] pioneered a culture protocol for the spheroid formation of the gastric corpus and body, which can be used as an in vitro model of H. pylori infection. Vlachogiannis et al[21] compared the responses of 21 patients with gastrointestinal tumors and patient-derived organoids (PDOs) to targeted drugs or chemotherapy and found that sensitivity and specificity to predict drug treatment for patients were 100% and 93%. Yan et al[9] established an organoid biobank and recorded differentially expressed genes between tumor organoids and paired tumor tissues. Seidlitz et al[22] and Nanki et al[23] demonstrated that human and mouse GC organoid models can mimic the typical human GC characteristics and altered signal pathways, demonstrating their potential role as biomarkers of treatment response.

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Figure 6 Milestone timeline in gastric organoid research. A chronological display of significant milestones in gastric organoid research, with each entry detailing a breakthrough and its impact on the field. PDO: Patient-derived organoids; GC: Gastric cancer; Hp: Helicobacter pylori; PSC: Pluripotent stem cell.

Burst analysis displayed the minimum duration of the bursts as 1 year, although the longest was 5 years. Of these citations, 28% (7/25) of the bursts occurred before 2015, with 36% (9/25) of literature bursts in 2015 and 36% (9/25) after 2017[24]. Twelve percent (3/25) of the citation outbreaks occurred in the past 2 years. Of the top 25 references, the strongest citation burst (14.3) was for studies by Barker et al[25], with the longest citation burst. Barker et al[25] reported that single Lgr5+ stem cells generated gastric-like organs in vitro and that the WNT pathway promoted Lgr5+ stem cell transformation, thereby promoting gastric adenoma formation. The second-highest citation burst appeared in a study by Stange et al[19], with a burst strength of 11.39 from 2015 to 2017. Stange et al[19] reported that Troy+ cells at the gland base can generate all gland cells, which represents remarkable plasticity ability in the field of epithelial stem cell biology. Molecular characterization of gastric adenocarcinoma also demonstrated a citation burst from 2018 to 2019, with a strength of 10.83[26]. In the past 2 years, Steel et al[27] reported that patient tissues exhibited a response to combination drug therapy similar to PDOs and PDOs, which resembled the original patient’s tissue gene mutation, which made a citation burst. Another review from Drost et al[28], which commented on current cancer organoid protocols and the method as a reliable model for cancer research also presented a burst. Figure 7 depicts the citation bursts for the 25 most-cited references.

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Figure 7 Top 25 references with the strongest citation bursts. This list showcases the most influential publications in gastric organoid research, with the strength of the citation bursts providing a quantitative measure of their impact over the years indicated.

This study conducts a comprehensive bibliometric analysis of gastric organoid research from 2010 to 2023, shedding light on its evolution and emerging trends.

To systematically map the progress and key developments in gastric organoid research, the study highlights the field’s significance.

To analyze and understand the development, impact, and direction of gastric organoid research using bibliometric methods.

Employed a combination of bibliometric tools and analytical techniques to assess publications and trends in gastric organoid research.

Identified key contributors and institutions in the field, highlighted the application of gastric organoids in studying gastric cancer and Helicobacter pylori-related gastritis.

The study underscores the critical role of gastric organoids in advancing our understanding of disease mechanisms and drug screening processes.

Future research should further explore the potential of gastric organoids in personalized medicine and enhance our comprehension of gastric diseases.