{"doi":"10.1089/scd.2011.0665","title":"Differentiation and Transplantation of Functional Pancreatic Beta Cells Generated from Induced Pluripotent Stem Cells Derived from a Type 1 Diabetes Mouse Model","abstract":"<jats:p>The nonobese diabetic (NOD) mouse is a classical animal model for autoimmune type 1 diabetes (T1D), closely mimicking features of human T1D. Thus, the NOD mouse presents an opportunity to test the effectiveness of induced pluripotent stem cells (iPSCs) as a therapeutic modality for T1D. Here, we demonstrate a proof of concept for cellular therapy using NOD mouse-derived iPSCs (NOD-iPSCs). We generated iPSCs from NOD mouse embryonic fibroblasts or NOD mouse pancreas-derived epithelial cells (NPEs), and applied directed differentiation protocols to differentiate the NOD-iPSCs toward functional pancreatic beta cells. Finally, we investigated whether the NPE-iPSC-derived insulin-producing cells could normalize hyperglycemia in transplanted diabetic mice. The NOD-iPSCs showed typical embryonic stem cell-like characteristics such as expression of markers for pluripotency, in vitro differentiation, teratoma formation, and generation of chimeric mice. We developed a method for stepwise differentiation of NOD-iPSCs into insulin-producing cells, and found that NPE-iPSCs differentiate more readily into insulin-producing cells. The differentiated NPE-iPSCs expressed diverse pancreatic beta cell markers and released insulin in response to glucose and KCl stimulation. Transplantation of the differentiated NPE-iPSCs into diabetic mice resulted in kidney engraftment. The engrafted cells responded to glucose by secreting insulin, thereby normalizing blood glucose levels. We propose that NOD-iPSCs will provide a useful tool for investigating genetic susceptibility to autoimmune diseases and generating a cellular interaction model of T1D, paving the way for the potential application of patient-derived iPSCs in autologous beta cell transplantation for treating diabetes.</jats:p>","journal":"Stem Cells and Development","year":2012,"id":589548,"datarank":2.8846341149611234,"base_score":4.61512051684126,"endowment":4.61512051684126,"self_citation_contribution":0.692268077526189,"citation_network_contribution":2.1923660374349345,"self_endowment_contribution":0.692268077526189,"citer_contribution":2.1923660374349345,"corpus_percentile":null,"corpus_rank":null,"citation_count":100,"citer_count":95,"citers_with_citation_signal":72,"citers_with_endowment":72,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1508388,"name":"Hyejin Lim","orcid":null,"position":1,"is_corresponding":false},{"id":112093,"name":"Jung-Hyun Kim","orcid":null,"position":2,"is_corresponding":false},{"id":1508389,"name":"Nguyen Van Thuan","orcid":null,"position":3,"is_corresponding":false},{"id":1508390,"name":"Seung Hwa Park","orcid":null,"position":4,"is_corresponding":false},{"id":1022376,"name":"Yu-Mi Lim","orcid":"0000-0001-8351-0564","position":5,"is_corresponding":false},{"id":1508391,"name":"Hye-Yeon Choi","orcid":null,"position":6,"is_corresponding":false},{"id":1508392,"name":"Eung-Ryoung Lee","orcid":null,"position":7,"is_corresponding":false},{"id":1508393,"name":"Jin-Hoi Kim","orcid":null,"position":8,"is_corresponding":false},{"id":1508394,"name":"Myung-Shik Lee","orcid":null,"position":9,"is_corresponding":false},{"id":211242,"name":"Ssang-Goo Cho","orcid":null,"position":10,"is_corresponding":false},{"id":520184,"name":"Kilsoo Jeon","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Differentiation and Transplantation of Functional Pancreatic Beta Cells Generated from Induced Pluripotent Stem Cells Derived from a Type 1 Diabetes Mouse Model","abstract":"<jats:p>The nonobese diabetic (NOD) mouse is a classical animal model for autoimmune type 1 diabetes (T1D), closely mimicking features of human T1D. Thus, the NOD mouse presents an opportunity to test the effectiveness of induced pluripotent stem cells (iPSCs) as a therapeutic modality for T1D. Here, we demonstrate a proof of concept for cellular therapy using NOD mouse-derived iPSCs (NOD-iPSCs). We generated iPSCs from NOD mouse embryonic fibroblasts or NOD mouse pancreas-derived epithelial cells (NPEs), and applied directed differentiation protocols to differentiate the NOD-iPSCs toward functional pancreatic beta cells. Finally, we investigated whether the NPE-iPSC-derived insulin-producing cells could normalize hyperglycemia in transplanted diabetic mice. The NOD-iPSCs showed typical embryonic stem cell-like characteristics such as expression of markers for pluripotency, in vitro differentiation, teratoma formation, and generation of chimeric mice. We developed a method for stepwise differentiation of NOD-iPSCs into insulin-producing cells, and found that NPE-iPSCs differentiate more readily into insulin-producing cells. The differentiated NPE-iPSCs expressed diverse pancreatic beta cell markers and released insulin in response to glucose and KCl stimulation. Transplantation of the differentiated NPE-iPSCs into diabetic mice resulted in kidney engraftment. The engrafted cells responded to glucose by secreting insulin, thereby normalizing blood glucose levels. We propose that NOD-iPSCs will provide a useful tool for investigating genetic susceptibility to autoimmune diseases and generating a cellular interaction model of T1D, paving the way for the potential application of patient-derived iPSCs in autologous beta cell transplantation for treating diabetes.</jats:p>","is_dataset_classified":null,"base_score":4.61512051684126,"endowment":4.61512051684126,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22512788","pmcid":"PMC3438879","openalex_id":"https://openalex.org/W1979457164","authors":[],"funders":[],"total_grants":0,"fwci":9.8115,"citation_percentile":0.98550125,"influential_citations":0,"citation_trend":[{"year":2012,"count":3},{"year":2013,"count":12},{"year":2014,"count":9},{"year":2015,"count":11},{"year":2016,"count":9},{"year":2017,"count":5},{"year":2018,"count":5},{"year":2019,"count":5},{"year":2020,"count":12},{"year":2021,"count":10},{"year":2022,"count":4},{"year":2023,"count":4},{"year":2024,"count":3},{"year":2025,"count":3},{"year":2026,"count":5}],"oa_status":"green","license":"https://journals.sagepub.com/page/policies/text-and-data-mining-license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3438879","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3438879","host_type":"repository"},{"url":"https://journals.sagepub.com/doi/full-xml/10.1089/scd.2011.0665","host_type":"publisher"},{"url":"https://journals.sagepub.com/doi/pdf/10.1089/scd.2011.0665","host_type":"publisher"},{"url":"https://doi.org/10.1089/scd.2011.0665","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22512788","host_type":"repository"},{"url":"http://europepmc.org/articles/PMC3438879","host_type":"repository"}],"fields_of_study":["Pancreatic function and diabetes","Pluripotent Stem Cells Research"],"mesh_terms":["Insulin Secretion","Animals","Blood Glucose","Cell Differentiation","Chimera","Diabetes Mellitus, Experimental","Female","Fibroblasts","Germ Layers","Glucose","Hyperglycemia","Insulin","Male","Mice, Inbred C57BL","Mice, Inbred ICR","Potassium Chloride","Streptozocin","Teratoma","Biomarkers","Mice, SCID","Mice, Inbred NOD","Gene Expression Profiling","Insulin-Secreting Cells","Mice","Embryonic Stem Cells","Induced Pluripotent Stem Cells"],"keywords":["Induced pluripotent stem cell","Nod","Biology","NOD mice","Embryonic stem cell","Transplantation","Cellular differentiation","Directed differentiation","Stem cell","Cell biology","Cancer research","Beta cell","Pancreas","Type 1 diabetes","Immunology","Insulin","Endocrinology","Diabetes mellitus","Internal medicine","Medicine","Genetics","Islet"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.12768649.v1","title":"Additional file 1 of Microencapsulation of cellular aggregates composed of differentiated insulin and glucagon-producing cells from human mesenchymal stem cells derived from adipose tissue","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.12768649","title":"Additional file 1 of Microencapsulation of cellular aggregates composed of differentiated insulin and glucagon-producing cells from human mesenchymal stem cells derived from adipose tissue","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-23T21:44:05.964129Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}