Abstract
Objectives
Induced pluripotent stem cells (iPSCs) have the potential to differentiate into insulin-producing β cells, offering a promising avenue for the treatment and research of diabetes. However, a comprehensive quantitative analysis of their specific impact in the field of diabetes has yet to be conducted. This study aims to analyze the current status and research hotspots of induced pluripotent stem cells in the field of diabetes over the past two decades, providing a reference for future research directions.
Methods
This study performed a bibliometric analysis of recent literature on induced pluripotent stem cells in the field of diabetes, with data sourced from the Web of Science database. Using R software and VOSviewer, keyword clustering and research themes were analyzed to uncover trends and frontiers in this field.
Results
The research included a total of 610 studies on induced pluripotent stem cells in the field of diabetes. In recent years, research in this field has shown a global upward trend, with the number of publications experiencing exponential growth from 2008 to 2021. However, the period from 2022 to 2025 is expected to be a plateau phase with fluctuations, gradually slowing down. The United States is the leading country in terms of publications, followed by China, Japan, the United Kingdom, and Italy. The United States not only leads in the number of publications but also has a broader network of international collaborators. Stem Cell Research and Diabetes are the most frequently published and cited journals. Currently, the application of iPSCs in studying the pathological mechanisms of diabetes and disease modeling has become a research hotspot. iPSCs provide an important in vitro platform for understanding the pathogenesis of diabetes and can also be used for drug screening, gene expression profiling, and studying the degeneration process of β-cells. Additionally, the use of iPSCs in the generation and regeneration of pancreatic β-cells, as a frontier of regenerative medicine and stem cell therapy, demonstrates the potential to restore normal islet function in diabetic patients. Furthermore, integrating immune evasion mechanisms and gene therapy, particularly by enhancing islet cell survival and function through immune regulation and genetic modification, is emerging as a new direction for diabetes treatment.
Conclusion
The differentiation of induced pluripotent stem cells into β cells may offer a pathway to curing diabetes. This article systematically analyzes the current status and research hotspots of induced pluripotent stem cells in the diabetes field, providing valuable references for future clinical practice and research.
Keywords: iPSC, Diabetes, Disease modeling, Gene therapy
1. Introduce
Diabetes is a group of metabolic disorders characterized by chronic hyperglycemia resulting from defects in insulin secretion or action [1]. Its prevalence is rising globally, and it is projected to reach 578 million people by 2030 [2], making it a major public health issue. Diabetes not only increases the risk of dying from cardiovascular diseases and stroke but can also lead to kidney damage, diabetic retinopathy, and neuropathy [3]. Additionally, hyperglycemia may cause complications such as diabetic foot, severely affecting patients' quality of life.
Since its introduction by Shinya Yamanaka in 2006, induced pluripotent stem cell (iPSC) technology has represented a significant breakthrough in stem cell research. By reprogramming somatic cells to a pluripotent state [4], iPSCs can differentiate into any cell type in the body, possessing characteristics similar to embryonic stem cells (ESCs), making them a valuable resource for regenerative medicine, disease modeling, and drug discovery [5]. The process of generating iPSCs involves resetting cell identity by introducing specific transcription factors (Yamanaka factors), allowing them to regain pluripotency [6]. iPSCs have become a revolutionary tool in regenerative medicine, particularly in the field of diabetes, as their ability to differentiate into insulin-producing β-cells offers promising avenues for treatment and research [7]. Compared to ESCs, iPSCs avoid ethical issues but still face challenges such as genomic instability and tumorigenicity. As research continues to address challenges associated with iPSC technology, the potential for these cells to revolutionize diabetes becomes increasingly apparent, and the future of diabetes treatment is likely to depend on the successful integration of iPSC technology into clinical practice.
Bibliometrics is a widely used method for analyzing academic publications, offering new researchers an overview of the evolution and frontiers of research fields [8]. Despite the steady increase in the number of related research papers, there is currently a lack of bibliometric analysis on induced pluripotent stem cells in the field of diabetes, leaving the knowledge system, research hotspots, and development trends in this area unclear. To address this gap, this study systematically analyzed the literature on induced pluripotent stem cells in the diabetes field over the past two decades using R software, VOSviewer, and CiteSpace. We aim to explore the changes in research hotspots and development trends in this field, providing guidance for potential directions and emerging areas for future research.
2. Materials and methods
2.1. Data collection
The data used in this study was retrieved and downloaded from the Web of Science Core Collection (WOSCC) database (version purchased by the General Hospital of the People's Liberation Army) on May 10, 2025. The following search formula was used: ((TS=(“IPS Cell∗” OR “Induced Pluripotent Stem Cell∗” OR “Fibroblast-Derived Induced Pluripotent Stem Cell∗” OR “Fibroblast Derived Induced Pluripotent Stem Cell∗” OR “Fibroblast-Derived IPS Cell∗” OR “Fibroblast Derived IPS Cell∗” OR “Human Induced Pluripotent Stem Cell∗”)) AND TS=(Diabetes mellitus OR Diabetes)) DT=(Article OR Review)) AND LA=(English). After excluding irrelevant literature, a total of 610 papers were identified (excluding duplicates). The retrieved papers were saved in plain text format and exported as complete records, including cited references.
2.2. Data analysis
To analyze the annual publications, Origin 2018 was used. Additionally, R software (version 4.5.0), Bibliometrix software (version 4.3.3), VOSviewer (version 1.6.18), and CiteSpace (version 6.4.R1) were employed for data visualization and the creation of scientific knowledge maps. To ensure data accuracy and reliability, data extraction and analysis management were independently completed by two different authors.
Bibliometrix software facilitated the visualization and mapping of scientific knowledge. VOSviewer was used to visualize the co-authorship network of countries and institutions, co-citation analysis of sources, and co-occurrence analysis of keywords. In the co-authorship network analysis, the following parameters were set: a minimum of 5 publications for a country and a minimum of 5 publications for an institution. For the co-citation analysis of sources, the parameter was set as follows: a minimum of 30 citations for a source. Furthermore, in the keyword co-occurrence analysis, the parameters were set as follows: a minimum occurrence of a keyword of 5, excluding keywords such as “Induced Pluripotent Stem Cell,” “Diabetes,” and their synonyms. The journal impact factors (IF) from the 2023 Journal Citation Reports (JCR) were retrieved.
3. Results
3.1. Review of induced pluripotent stem cell and diabetes
After removing duplicates, a total of 610 unique records were obtained from WoSCC. As shown in Fig. 1A, from 2008 to 2021, the number of publications on induced pluripotent stem cells in the field of diabetes research exhibited an exponential growth trend. However, from 2022 to 2025, there is a plateau period with fluctuations, indicating a gradual slowdown. This upward trend reflects a growing research interest in exploring the application of induced pluripotent stem cells in diabetes, although there are recent bottlenecks and technical challenges that need to be addressed.
Fig. 1.
Annual publication trends in the area of the induced pluripotent stem cells in the field of diabetes. (A) Trends in publication results by year. (B) Country and collaboration distribution of corresponding authors.
An analysis of the countries of the corresponding authors reveals that the United States (n = 171) is the leading publishing country, followed by China (n = 84), Japan (n = 75), the United Kingdom (n = 25), and Italy (n = 24). Additionally, 21.1 % of the publications from the United States and 19 % from China involve multi-country collaborations (MCPs), as shown in Fig. 1B and detailed in Table 1. It is noteworthy that the United States not only leads in the number of publications but also has a broader network of international partners, as shown in Fig. 2A. Furthermore, the collaboration map indicates that Harvard University (n = 22) and Kyoto University (n = 22) are key collaboration centers (Fig. 2B; Table 2).
Table 1.
Most relevant countries by corresponding authors.
| Country | Articles | Articles % | SCP | MCP | MCP % |
|---|---|---|---|---|---|
| USA | 171 | 28 | 135 | 36 | 21.1 |
| CHINA | 84 | 13.8 | 68 | 16 | 19 |
| JAPAN | 75 | 12.3 | 69 | 6 | 8 |
| UNITED KINGDOM | 25 | 4.1 | 11 | 14 | 56 |
| ITALY | 24 | 3.9 | 17 | 7 | 29.2 |
| GERMANY | 20 | 3.3 | 13 | 7 | 35 |
| KOREA | 20 | 3.3 | 18 | 2 | 10 |
| IRAN | 19 | 3.1 | 17 | 2 | 10.5 |
| BELGIUM | 18 | 3 | 7 | 11 | 61.1 |
| SINGAPORE | 16 | 2.6 | 13 | 3 | 18.8 |
| CANADA | 14 | 2.3 | 8 | 6 | 42.9 |
| FRANCE | 13 | 2.1 | 4 | 9 | 69.2 |
| QATAR | 13 | 2.1 | 8 | 5 | 38.5 |
| INDIA | 9 | 1.5 | 9 | 0 | 0 |
| FINLAND | 8 | 1.3 | 4 | 4 | 50 |
| AUSTRALIA | 7 | 1.1 | 3 | 4 | 57.1 |
| IRELAND | 7 | 1.1 | 2 | 5 | 71.4 |
| RUSSIA | 7 | 1.1 | 7 | 0 | 0 |
| SWITZERLAND | 6 | 1 | 3 | 3 | 50 |
| NORWAY | 5 | 0.8 | 1 | 4 | 80 |
Fig. 2.
Map of countries/regions and organizations in the field of the relationship between the induced pluripotent stem cells and diabete. (A) Map of cooperation between different countries. (B) Map of cooperation between different institutions.
Table 2.
Most relevant affiliations.
| Affiliation | Articles (n) |
|---|---|
| Harvard University | 22 |
| Kyoto University | 22 |
| National University of Singapore | 17 |
| Stanford University | 17 |
| Harvard Medical School | 15 |
| Free University of Brussels | 14 |
| The University of Tokyo | 14 |
| University of Oxford | 13 |
| Mayo clinic | 12 |
| University of California, San Francisco | 11 |
| University of Pisa | 11 |
| Nanyang Technological University | 10 |
| University of Washington | 10 |
| ASTAR | 9 |
| Columbia University in the City of New York | 9 |
| Haukeland University Hospital | 8 |
| Islamic Azad University | 8 |
| University of Bergen | 8 |
| University of California, Los Angeles | 8 |
| University of Helsinki | 8 |
These data suggest that the United States is globally leading in terms of publication volume and academic influence, holding a significant advantage. China is in a phase of rapid catch-up, possibly driven by policy initiatives. Although the number of papers from Japan is not as high as those from the US and China, Japan excels in original research, supported by institutions such as Kyoto University.
3.2. Journals and co-cited journals
Using R software (version 4.5.0) along with the Bibliometrix and ggplot2 packages, we analyzed the journals with the highest number of published articles and citations in this field. Additionally, we used VOSviewer (version 1.6.18) to conduct a co-citation analysis of the journals, which revealed that a total of 610 papers were published across 276 academic journals (see Supplementary Material 1 for details). As shown in Table 3 and Fig. 3A, Stem Cell Research (n = 32, IF = 0.8) emerged as the leading publisher, followed by Scientific Reports (n = 23, IF = 3.8), Stem Cell Research & Therapy (n = 20, IF = 7.1), Diabetologia (n = 18, IF = 8.4), and Diabetes (n = 13, IF = 6.2). Table 4 and Fig. 3B display the most cited journals, including Diabetes (n = 1953, IF = 6.2), Nature (n = 1464, IF = 50.5), Nature Biotechnology (n = 1290, IF = 33.1), Proceedings of the National Academy of Sciences of the United States of America (n = 1278, IF = 9.4), and Cell (n = 1210, IF = 45.6). Notably, the co-cited journals shown in Fig. 4 indicate that Diabetes, PLOS ONE, and Nature serve as core collaborative hubs. These findings collectively emphasize the influence of Diabetes in the field of induced pluripotent stem cell diabetes research.
Table 3.
Top 10 journals with the most published.
| Journal | Articles | IF | Cites |
|---|---|---|---|
| Stem Cell Research | 32 | 0.8 | 303 |
| Scientific Reports | 23 | 3.8 | 463 |
| Stem Cell Research & Therapy | 20 | 7.1 | 225 |
| Diabetologia | 18 | 8.4 | 884 |
| Diabetes | 13 | 6.2 | 1953 |
| IJMS | 12 | 4.9 | 194 |
| Plos One | 12 | 2.9 | 745 |
| Nature Communications | 11 | 14.7 | 497 |
| Frontiers in Endocrinology | 10 | 3.9 | 118 |
| Stem Cell Reviews and Reports | 9 | 4.5 | 148 |
Fig. 3.
Journals with the most published and journals with the most cited (A) Journals with the most published (B) Journals with the most cited.
Table 4.
Top 10 journals with the most cited.
| Journal | Cites | IF | Articles |
|---|---|---|---|
| Diabetes | 1953 | 6.2 | 13 |
| Nature | 1464 | 50.5 | 3 |
| Nature Biotechnology | 1290 | 33.1 | 1 |
| PNAS | 1278 | 9.4 | 7 |
| Cell | 1210 | 45.6 | 2 |
| Cell Stem Cell | 995 | 19.8 | 2 |
| Diabetologia | 884 | 8.4 | 18 |
| Science | 788 | 44.8 | 0 |
| Stem Cells | 768 | 4 | 4 |
| Plos One | 745 | 2.9 | 12 |
Fig. 4.
Co-citation journals in the field of induced pluripotent stem cells and diabete.
3.3. Most cited references and reference burst
We used the Bibliometrix package in R software to identify the top 20 most cited papers in the field of induced pluripotent stem cells for diabetes research (Table 5). Each of these papers has been cited over 125 times and spans 17 different journals, indicating that many significant breakthroughs are still emerging in this field. Interestingly, no single journal dominates among the top 20 most cited papers.
Table 5.
Top 20 cited references.
| DOI | Total Citations | TC per Year |
|---|---|---|
| 10.1016/j.cell.2008.07.041 | 1710 | 95.00 |
| 10.1038/nature09691 | 1441 | 96.07 |
| 10.1038/cr.2009.28 | 452 | 26.59 |
| 10.1073/pnas.0906894106 | 433 | 25.47 |
| 10.1210/er.2008-0031 | 359 | 21.12 |
| 10.1074/jbc.M806597200 | 283 | 15.72 |
| 10.1172/JCI88648 | 228 | 25.33 |
| 10.1038/s41586-020-2631-z | 225 | 37.50 |
| 10.1186/s13287-017-0694-z | 219 | 24.33 |
| 10.1016/j.molmet.2017.06.001 | 207 | 23.00 |
| 10.1016/j.celrep.2014.09.055 | 198 | 16.50 |
| 10.1073/pnas.1007884107 | 189 | 11.81 |
| 10.1016/j.scr.2011.10.002 | 179 | 12.79 |
| 10.1007/s00125-011-2283-5 | 169 | 11.27 |
| 10.1016/j.cmet.2017.08.007 | 166 | 20.75 |
| 10.1039/c8lc01298a | 150 | 21.43 |
| 10.1242/jcs.114827 | 138 | 9.86 |
| 10.1038/nature13287 | 135 | 11.25 |
| 10.5966/sctm.2012-0116 | 125 | 9.62 |
| 10.7554/eLife.00940 | 125 | 9.62 |
The most cited papers include “Disease-specific induced pluripotent stem cells?”, “Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro,” and “Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells.” These articles are primarily original research and review articles on induced pluripotent stem cells in the field of diabetes.
To further explore the frontiers and key areas of induced pluripotent stem cell research in diabetes, we used CiteSpace to identify 165 references with significant citation bursts based on specific criteria (top 25; status count: 2; minimum duration: 2), with 25 of them showcased in Fig. 5. Identify the top 25 most significant citation bursts related to the field of induced pluripotent stem cells in diabetes (see Fig. 5). Notably, the three citations with the most significant bursts are: “Generation of Functional Human Pancreatic β Cells In Vitro (intensity: 34.88)”; “Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells (intensity: 32.46)”; “Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo (intensity: 22.52)”; Additionally, the three most cutting-edge citation bursts are titled: “Generation of insulin-producing pancreatic β cells from multiple human stem cell lines”; “Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes”; “Functional, metabolic, and transcriptional maturation of human pancreatic islets derived from stem cells”.
Fig. 5.
The 25 most cited references in areas related to the induced pluripotent stem cells and diabete.
Overall, through the analysis of the most cited literature and citation bursts, we have identified four key research directions in the field of induced pluripotent stem cells in diabetes: 1. Application of induced pluripotent stem cells (iPSCs) in diabetes treatment; 2. Modeling and research of diabetes pathomechanisms using iPSCs; 3. Application of iPSCs in the generation and regeneration of pancreatic β cells; 4. Combined application of iPSCs and immune evasion mechanisms.
3.4. Keyword clusters and evolution
Keyword groups are crucial for quickly understanding the main research themes and directions in a specific field. In our study, 2,430 keywords were identified using VOSviewer. Table 6 shows the top 20 keywords that appeared more than 35 times, highlighting the main research focuses. “Differentiation” (n = 173) is the most frequently occurring keyword, followed by “generation” (n = 157), “beta cell” (n = 131), “in-vitro” (n = 124), “insulin producing cells” (n = 120), and “expression” (n = 85).
Table 6.
The top 20 keywords.
| rank | words | count |
|---|---|---|
| 1 | Differentiation | 173 |
| 2 | Generation | 157 |
| 3 | Beta cell | 131 |
| 4 | In-vitro | 124 |
| 5 | Insulin producing cells | 120 |
| 6 | Expression | 85 |
| 7 | Progenitor | 82 |
| 8 | Mouse | 70 |
| 9 | Embryonic stem cell | 64 |
| 10 | Pancreatic beta cell | 64 |
| 11 | Type 1 diabetes | 64 |
| 12 | Efficient differentiation | 56 |
| 13 | Transplantation | 54 |
| 14 | Induction | 50 |
| 15 | Islet transplantation | 50 |
| 16 | Insulin | 48 |
| 17 | Maturation | 41 |
| 18 | Gene | 39 |
| 19 | Transcription factor | 37 |
| 20 | Pancreatic progenitor cells | 36 |
Through cluster analysis, we observed four distinct colored clusters in Fig. 6. (1) The integration of molecular mechanisms of diabetes with regenerative medicine treatments, comprising 74 keywords, including retinopathy, molecular mechanisms, diabetic cardiomyopathy, oxidative stress, mitochondrial dysfunction, etc. (2) The application of stem cell therapy and regenerative medicine in diabetes treatment (green dots), with 54 keywords, including efficient differentiation, pancreatic beta cell, islet transplantation, insulin secretion, stem cell therapy, etc. (3) Mechanisms of induced pluripotent stem cell differentiation into pancreatic β-cells and their application in diabetes treatment (blue dots), with 31 keywords, including pancreatic progenitor cells, induction, pancreatic differentiation, islet, transcription, etc. (4) Utilizing regenerative medicine and gene therapy to harness the potential of stem cells to restore islet function and cure or improve diabetes (yellow dots), with 17 keywords, including cell therapy, reprogramming, fibroblasts, islet-like clusters, efficient generation. All keywords contained in the four clusters can be found in Supplementary Material 2.
Fig. 6.
Keyword co-occurrence map of papers in areas related to the induced pluripotent stem cells and diabete.
In addition, to predict upcoming trends in this field, we utilized bibliometric packages in the R programming environment to construct a dynamic thematic progression map (Fig. 7). Between 2010 and 2014, the research primarily focused on stem cell differentiation and islet transplantation. During this period, studies explored the mechanisms related to islet generation and emphasized the potential of different types of stem cells for generating islet β-cells, particularly the application of embryonic stem cells and mouse models. After 2015, research began to concentrate on the more detailed generation and function of islet cells, especially islet-like clusters and β-cells. Additionally, research started to cover topics related to gene therapy and directed differentiation, utilizing these strategies to more efficiently generate cells with islet functions, further providing possible clinical pathways for diabetes treatment. From 2019 to 2022, the research focus gradually shifted to pancreas development, endocrine cells, and the application of induced pluripotent stem cells (iPS cells) in diabetes treatment. Furthermore, researchers are increasingly focusing on the role of small molecules and transcription factors in enhancing the efficiency and quality of stem cell differentiation. Current research hotspots continue to concentrate on efficient differentiation, epigenetic memory, and the functional restoration of insulin-producing cells. As stem cell research progresses, more studies are beginning to explore specific mechanisms such as microRNA (miRNA) and mouse models, aiming to improve the success rate and clinical applicability of stem cell therapy for diabetes.
Fig. 7.
Trending topics in areas related to the induced pluripotent stem cells and diabete.
3.5. Hotspot analysis
In summary, our comprehensive analysis, which includes citation bursts, keyword frequency analysis, keyword clustering, and thematic evolution, has identified emerging research hotspots in the field of induced pluripotent stem cell diabetes. Our findings indicate that the research hotspots in this field mainly focus on three key directions. (1) The application of iPSCs in studying the pathological mechanisms and disease modeling of diabetes. (2) The application of iPSCs in the generation and regeneration of pancreatic β-cells. (3) The combined application of iPSCs with immune evasion mechanisms and gene therapy.
4. Discussion
4.1. General information
In this study, we collected 610 publications indexed in the Web of Science. The results show that from 2008 to 2021, the number of publications on induced pluripotent stem cells in diabetes research exhibited an exponential growth trend. However, from 2022 to 2025, this trend entered a period of fluctuation, gradually slowing down. This phenomenon can be attributed to the following reasons: From 2009 to 2012, breakthroughs in non-integrating vector technology, such as the optimization of reprogramming methods by Shinya Yamanaka's team [6], allowed iPSCs to gradually transition from the laboratory to disease modeling. From 2014 to 2018, the synergistic application of 3D organoids and CRISPR editing technology [9] facilitated the annual publication volume to exceed 50 papers. In 2019, ethical controversies over human-animal chimeras (leading to Japan suspending experiments) and issues of epigenetic memory retention caused a decline in publication volume. In 2021, AI technology predicted β-cell differentiation factors, driving the publication volume to a peak of 64 papers. However, in 2023, it dropped sharply to 41 papers due to disruptions in the COVID-19 supply chain and the impact of new FDA cell purity regulations. In 2024, breakthroughs in clinical translation (the success of Vertex's VX-880 therapy Phase III) and epigenome erasure technology led to a rebound in publication volume to 54 papers.
A total of 610 publications were distributed across 276 journals, with well-known journals such as Stem Cell Research, Scientific Reports, Stem Cell Research & Therapy, Diabetologia, and Diabetes contributing a large number of articles. It is noteworthy that Diabetes has become a major research focus, with a large number of articles published and a considerable number of citations received. Its prominent status underscores Diabetes as a key publication in the field of induced pluripotent stem cell diabetes, affirming its role as a primary channel for disseminating research findings in this area.
4.2. Hotspots and development trends
Through a comprehensive analysis of literature clustering, keyword frequency, keyword clustering, and thematic evolution, we have identified potential hotspots in the field of induced pluripotent stem cells (iPSCs) for diabetes. The results indicate that the research frontiers and hotspots in this field mainly focus on the following three aspects. Firstly, the application of iPSCs in studying the pathological mechanisms of diabetes and disease modeling. iPSCs can be used for drug screening, understanding related gene expression characteristics, and the process of β-cell degradation. Secondly, the application of iPSCs in the generation and regeneration of pancreatic β-cells is also a current hotspot in regenerative medicine and stem cell therapy, which can help restore normal islet function in diabetic patients. Finally, the combined application of iPSCs with immune evasion mechanisms and gene therapy, particularly through immune regulation and gene modification to improve islet cell survival and function, is emerging as a new direction in diabetes treatment research.
4.2.1. Application of iPSCs in the study of pathological mechanisms and disease modeling of diabetes
iPSC technology provides a powerful tool for studying the pathological mechanisms and disease modeling of diabetes. A key feature of type 1 and type 2 diabetes is pancreatic β-cell dysfunction. iPSC-derived β-like cells can mimic β-cell functional abnormalities such as impaired insulin secretion, increased apoptosis, and reduced glucose responsiveness, thereby helping to reveal molecular pathways and cellular processes in diabetic β-cells [[10], [11], [12], [13]], providing a basis for the development of targeted therapies. Meanwhile, insulin resistance in type 2 diabetes can be studied through iPSC technology by generating functional hepatocytes [14], myocytes [15], and adipocytes [16,17], exploring mechanisms such as lipid accumulation, endoplasmic reticulum stress, and impaired glucose uptake. In addition, iPSC technology can be utilized to study the impact of specific gene mutations on the development of diabetes. This can be achieved by generating iPSCs from patients with monogenic diabetes and employing CRISPR-Cas9 technology for gene editing to investigate the effects of mutations on β-cell function [18,19]. iPSC technology can also be applied to model diabetic complications. For example, by differentiating iPSCs into endothelial cells, neurons, and cardiomyocytes, researchers can study the mechanisms of long-term complications such as diabetic retinopathy [[20], [21], [22]], neuropathy [23], and cardiomyopathy [24,25], thereby providing important experimental models for identifying potential therapeutic targets.
Although iPSCs have broad application prospects in the field of diabetes, challenges remain. iPSC-derived diabetic cell models can simulate certain pathological processes, but they still cannot fully replicate the complex microenvironment and intercellular interactions present in vivo. This may lead to limitations in the reliability and reproducibility of the models compared to in situ tissues. Future research will focus on further developing technologies such as 3D cell culture [26], organoid models, and microfluidics [27] to better replicate the complex biological environment in vivo with iPSC-derived diabetic models, thereby enhancing the accuracy and reproducibility of research.
4.2.2. Applications of iPSCs in the generation and regeneration of pancreatic β cells
The application of iPSC technology in the generation and regeneration of pancreatic β cells holds significant research value. By optimizing differentiation protocols, iPSCs can be effectively differentiated into functional pancreatic β cells and utilized to repair damaged cells. Vertex's VX-880 [28] is the world's first islet β-cell therapy based on induced pluripotent stem cells (iPSC). In December 2023, the first successful cure was reported, marking a shift in diabetes treatment from “insulin replacement” to the era of “functional cure.” Meanwhile, in China, Shanghai Changzheng Hospital, in collaboration with the Chinese Academy of Sciences, successfully cured a case of severely impaired islet function in type 2 diabetes using autologous regenerative islet transplantation derived from stem cells [29]. On February 12, 2025, Kyoto University completed the world's first clinical transplantation surgery for type 1 diabetes based on iPSCs, using a “universal cell bank + pre-vascularized transplantation” model, reducing the cost of a single treatment course. This groundbreaking surgery marks the transition of iPSC treatment from technical verification to industrial application.
However, iPSCs still face challenges in application, particularly the risk of teratoma formation [30,31], which requires ensuring complete differentiation into functional β cells before transplantation. Moreover, optimizing the differentiation process to improve the yield and function of β cells remains a key research direction. Strategies involving small molecules that promote the proliferation of pancreatic progenitor cells, such as AT7867 [32], have shown potential in enhancing the proliferation of these cells, providing new prospects for cellular therapy of type 1 diabetes.
4.2.3. The combined application of iPSCs with immune evasion mechanisms and gene therapy
The application of iPSC technology in diabetes treatment, especially in conjunction with immune evasion mechanisms and gene therapy, shows great potential. Research has revealed that iPSCs can regulate immune responses through gene expression [33,34], enhancing immune tolerance and reducing the likelihood of immune attacks on β cells, thereby achieving long-term effective diabetes treatment. This provides a theoretical foundation for the application of iPSC-derived therapies. In the field of gene therapy, iPSCs offer a unique opportunity to correct genetic defects, but they also face potential risks such as oncogene activation and leukemogenesis. To address these challenges, immune evasion strategies, such as engineering iPSCs to express immune checkpoint inhibitors [[35], [36], [37]], have become key methods to enhance immune tolerance and reduce rejection. Recent advances in iPSC technology, including CRISPR-Cas9 gene editing [18,19] and extracellular vesicle RNA therapy [[38], [39], [40]], have further enhanced their immune evasion capabilities, providing new directions for gene therapy.
However, the challenge of combining iPSCs with immune evasion mechanisms lies in the risk of tumorigenesis and the complexity of immune responses, necessitating in-depth research into their molecular mechanisms and the interaction between the immune system and the host. Future research should focus on improving the safety and efficacy of iPSC therapies, exploring the synergistic effects of epigenetic modifications and immunotherapy, thereby providing safer and more effective solutions for the treatment of diabetes and other diseases.
4.3. Limitations
The study uses the WoSCC database as a data source, offering a comprehensive overview of the field, including its overall scope, key areas, and research trends. This approach facilitates a deeper understanding of the field and aids in exploring future research directions. However, the study has some significant limitations. Firstly, relying solely on the WoSCC database may result in missing some relevant publications, even though the database is of high quality and widely considered an ideal tool for bibliometric analysis. Secondly, the study only includes publications in English, which may introduce language bias and limit the generalizability of the research findings. Despite these limitations, the study's conclusions remain highly reliable and provide valuable insights and references for academic research in the field.
5. Conclusion
This study systematically reveals the main research hotspots and frontiers of induced pluripotent stem cells (iPSCs) in the field of diabetes, summarized as follows: Stem Cell Research and Diabetes are the most frequently published and cited journals. The current research hotspots mainly focus on the application of iPSCs in studying the pathological mechanisms and disease modeling of diabetes. iPSCs not only provide an important in vitro platform for understanding the pathogenesis of diabetes but also can be used for drug screening, understanding related gene expression characteristics, and the process of β-cell degeneration. The use of iPSCs in the generation and regeneration of pancreatic β-cells is also a current focus in regenerative medicine and stem cell therapy, capable of restoring normal islet function in diabetic patients. The integration of iPSCs with immune evasion mechanisms and gene therapy, particularly through immune regulation and genetic modification to enhance the survival and function of islet cells, is emerging as a new direction in diabetes treatment research.
-
a
Research on the association of induced pluripotent stem cells in the field of diabetes has garnered widespread attention from scholars worldwide. The United States, China, Japan, the United Kingdom, and Italy are the most active countries in this field, engaging in close and extensive international collaboration.
-
b
Stem Cell Research, Scientific Reports, Stem Cell Research & Therapy, Diabetologia, and Diabetes are the journals with the most publications in this field. Notably, Diabetes has become a representative journal due to its high citation rate.
-
c
The application of iPSCs in studying the pathological mechanisms and disease modeling of diabetes is a key research focus.
-
d
The use of iPSCs in the generation and regeneration of pancreatic β-cells can restore normal islet function in diabetic patients, which is currently a prominent trend in diabetes research.
-
e
The integration of iPSCs with immune evasion mechanisms and gene therapy represents a new direction in diabetes treatment research.
In summary, this study provides in-depth and valuable insights into the research trends and hotspots in the field of induced pluripotent stem cells and diabetes. These findings not only equip researchers with the necessary background knowledge for a comprehensive understanding of the field but also lay the foundation for exploring new research directions. By identifying current research frontiers and potential key areas, our study offers strong support and guidance for future innovative research.
Ethics approval and consent to participate
Not applicable.
Consent for publication
Consent for publication was obtained from the participants.
Data availability statement
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
Author’s contributions
Jiatong Wang: Writing-original draft preparation, Writing-review&editing, Visualization, Investigation, Formal analysis, Data curation, Methodology, Conceptualization. Sirui Huang: Writing-review&editing, Investigation, Software, Visualization, Data curation. Kaiyuan Li: Writing - review & editing. Jing Li: Writing - review & editing, Project administration, Resources, Supervision. Xin Huang: Writing-review &editing, Methodology, Conceptualization.
Funding
Our study did not receive a grant for our article.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Footnotes
Peer review under responsibility of the Japanese Society for Regenerative Medicine.
Supplementary data to this article can be found online at https://doi.org/10.1016/j.reth.2025.06.015.
Appendix A. Supplementary data
The following are the Supplementary data to this article.
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Supplementary Materials
Data Availability Statement
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.