ArticleNature protocols2021
Generation of insulin-producing pancreatic β cells from multiple human stem cell lines.
Article in Nature protocols, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
137 citing papers in PubMed, 1 synthesis or guideline pooled it, 189 citations in OpenAlex.
- Development and trend of stem cell therapy for diabetes: a comprehensive review based on knowledge visualization.Frontiers in immunology · 2026Pooled it
- ProtectiveiScience · 2026Article
- Predictive control of human pancreatic cell fate using a digital model ofbioRxiv : the preprint server for biology · 2026Article
- The comparative cell physiology of stem cell-derived and primary human β cells.Nature reviews. Endocrinology · 2026Review
- A Stepwise Method to Derive Functional Pancreatic Islet-like Clusters from Human Pluripotent Stem Cells.Current protocols · 2026Article
- Metabolic Programming of β-Cell Fate, State, and Function through Time and Space.Physiology (Bethesda, Md.) · 2026Review
- Biofabrication for spatial control of multiscale biological crosstalk in tissue models.npj biomedical innovations · 2026Review
- Stem cell therapies for treatment of diabetes mellitus.Chinese medical journal · 2026Review
- Protocol to stress human primary pancreatic islets with diabetogenic factors for subsequent single-cell RNA sequencing.STAR protocols · 2026Article
- MAFB in Pancreatic β-Cell Development and Dysfunction: Implications for Diabetes and Translational Applications.Biomolecules · 2026Review
- Application of human induced pluripotent stem cells for tissue modeling and therapy: are we on track?Stem cells (Dayton, Ohio) · 2026Review
- Allogeneic islet products for type 1 diabetes: Navigating nonclinical and manufacturing regulatory expectations.Stem cell reports · 2026Review
- Review
- Stem cell-based therapies for type 1 diabetes: Progress in differentiation, clinical translation, and immune protection.Animal models and experimental medicine · 2026Review
- Pancreatic organoids and organoid-on-a-chip platforms: from disease modeling to precision therapy.Journal of translational medicine · 2026Review
- SOX9: dosage- and context-dependent functions in pancreatic development and β-cell biology.Cell communication and signaling : CCS · 2026Review
- A dish-to-biobank framework links β-cell nutrient-stress programs to genetic and dietary risk for Type 2 Diabetes.bioRxiv : the preprint server for biology · 2026Article
- Small molecules promote the in vitro expansion and passaging of adult mouse pancreatic islets.Biochemistry and biophysics reports · 2026Article
- Real-time in vivo analysis of murine β cells reveals autophagic flux defects before onset of autoimmune diabetes.Science translational medicine · 2026Article
- Clinical translational research on stem cell products: prospects and challenges.Signal transduction and targeted therapy · 2026Review
77 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We detail a six-stage planar differentiation methodology for generating human pluripotent stem cell-derived pancreatic β cells (SC-β cells) that secrete high amounts of insulin in response to glucose stimulation. This protocol first induces definitive endoderm by treatment with Activin A and CHIR99021, then generates PDX1+/NKX6-1+ pancreatic progenitors through the timed application of keratinocyte growth factor, SANT1, TPPB, LDN193189 and retinoic acid. Endocrine induction and subsequent SC-β-cell specification is achieved with a cocktail consisting of the cytoskeletal depolymerizing compound latrunculin A combined with XXI, T3, ALK5 inhibitor II, SANT1 and retinoic acid. The resulting SC-β cells and other endocrine cell types can then be aggregated into islet-like clusters for analysis and transplantation. This differentiation methodology takes ~34 d to generate functional SC-β cells, plus an additional 1-2 weeks for initial stem cell expansion and final cell assessment. This protocol builds upon a large body of previous work for generating β-like cells. In this iteration, we have eliminated the need for 3D culture during endocrine induction, allowing for the generation of highly functional SC-β cells to be done entirely on tissue culture polystyrene. This change simplifies the differentiation methodology, requiring only basic stem cell culture experience as well as familiarity with assessment techniques common in biology laboratories. In addition to expanding protocol accessibility and simplifying SC-β-cell generation, we demonstrate that this planar methodology is amenable for differentiating SC-β cells from a wide variety of cell lines from various sources, broadening its applicability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.