ArticleProceedings of the National Academy of Sciences of the United States of America2000
In vitro cultivation of human islets from expanded ductal tissue.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 272 papers.
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Who cites it
272 citing papers in PubMed, 973 citations in OpenAlex.
- Novel therapy for insulin-dependent diabetes mellitus: infusion of in vitro-generated insulin-secreting cells.Clinical and experimental medicine · 2015Trial
- Purified human pancreatic duct cell culture conditions defined by serum-free high-content growth factor screening.PloS one · 2012Trial
- Review
- Advances in liver and pancreas organoids: how far we have come and where we go next.Nature reviews. Gastroenterology & hepatology · 2026Review
- Mechanisms inducing differentiation of adult islet progenitor-like cells into functional islet-like organoids.Frontiers in transplantation · 2026Article
- A Protocol for the In Vitro Culturing of Vascularized Pancreatic Islet Organoids.Bioengineering (Basel, Switzerland) · 2025Article
- Article
- Pancreatic Ductal Cell Heterogeneity: Insights into the Potential for β-Cell Regeneration in Diabetes.Stem cell reviews and reports · 2025Review
- Loss of insulin-expressing extra-islet cells in type 1 diabetes is accompanied with increased number of glucagon-expressing extra-islet cells.Virchows Archiv : an international journal of pathology · 2025Article
- In Vivo Differentiation of Endogenous Bone Marrow-Derived Cells into Insulin-Producing Cells Using Four Soluble Factors.Diabetes & metabolism journal · 2025Article
- Differentiation, reduction, and proliferation of pancreatic β-cells and their regulatory factors.Diabetology international · 2025Review
- Engineered tools to study endocrine dysfunction of pancreas.Biophysics reviews · 2024Review
- Rare, Tightly-Bound, Multi-Cellular Clusters in the Pancreatic Ducts of Adult Mice Function Like Progenitor Cells and Survive and Proliferate After Acinar Cell Injury.Stem cells (Dayton, Ohio) · 2024Article
- Advanced therapy to cure diabetes: mission impossible is now possible?Frontiers in cell and developmental biology · 2024Review
- β-Cell Heterogeneity and Plasticity.Advances in anatomy, embryology, and cell biology · 2024Review
- Emerging therapeutic options in the management of diabetes: recent trends, challenges and future directions.International journal of obesity (2005) · 2023Review
- Matters arising: Insufficient evidence that pancreatic β cells are derived from adult ductal Neurog3-expressing progenitors.Cell stem cell · 2023Article
- Methylcellulose colony assay and single-cell micro-manipulation reveal progenitor-like cells in adult human pancreatic ducts.Stem cell reports · 2023Article
- Direct Reprogramming of Somatic Cells into Induced β-Cells: An Overview.Advances in experimental medicine and biology · 2023Article
- Direct Reprogramming of Different Cell Lineages into Pancreatic β-Like Cells.Cellular reprogramming · 2022Review
212 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A major obstacle to successful islet transplantation for both type 1 and 2 diabetes is an inadequate supply of insulin-producing tissue. This need for transplantable human islets has stimulated efforts to expand existing pancreatic islets and/or grow new ones. To test the hypothesis that human adult duct tissue could be expanded and differentiated in vitro to form islet cells, digested pancreatic tissue that is normally discarded from eight human islet isolations was cultured under conditions that allowed expansion of the ductal cells as a monolayer whereupon the cells were overlaid with a thin layer of Matrigel. With this manipulation, the monolayer of epithelial cells formed three-dimensional structures of ductal cysts from which 50-to 150- micrometer diameter islet-like clusters of pancreatic endocrine cells budded. Over 3-4 weeks culture the insulin content per flask increased 10- to 15-fold as the DNA content increased up to 7-fold. The cultivated human islet buds were shown by immunofluorescence to consist of cytokeratin 19-positive duct cells and hormone-positive islet cells. Double staining of insulin and non-beta cell hormones in occasional cells indicated immature cells still in the process of differentiation. Insulin secretion studies were done over 24 h in culture. Compared with their basal secretion at 5 mM glucose, cysts/cultivated human islet buds exposed to stimulatory 20 mM glucose had a 2.3-fold increase in secreted insulin. Thus, duct tissue from human pancreas can be expanded in culture and then be directed to differentiate into glucose responsive islet tissue in vitro. This approach may provide a potential new source of pancreatic islet cells for transplantation.
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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.