ArticleDiabetologia2016
Effective endothelial cell and human pluripotent stem cell interactions generate functional insulin-producing beta cells.
Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
What it found
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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
15 citing papers in PubMed, 23 citations in OpenAlex.
- Pancreatic organoids and organoid-on-a-chip platforms: from disease modeling to precision therapy.Journal of translational medicine · 2026Review
- Investigational New Drug-enabling studies in a human vessel-chip: Are we there yet?Bioengineering & translational medicine · 2026Review
- A Protocol for the In Vitro Culturing of Vascularized Pancreatic Islet Organoids.Bioengineering (Basel, Switzerland) · 2025Article
- Bioprinting of bespoke islet-specific niches to promote maturation of stem cell-derived islets.Nature communications · 2025Article
- The role of endothelial cells in pancreatic islet development, transplantation and culture.Frontiers in cell and developmental biology · 2025Review
- Endothelial-derived angiocrine factors as instructors of embryonic development.Frontiers in cell and developmental biology · 2023Review
- Glucose-Dependent Insulin Secretion from β Cell Spheroids Is Enhanced by Embedding into Softer Alginate Hydrogels Functionalised with RGD Peptide.Bioengineering (Basel, Switzerland) · 2022Article
- Human pancreatic microenvironment promotes β-cell differentiation via non-canonical WNT5A/JNK and BMP signaling.Nature communications · 2022Article
- Making human pancreatic islet organoids: Progresses on the cell origins, biomaterials and three-dimensional technologies.Theranostics · 2022Review
- Engineering islets from stem cells for advanced therapies of diabetes.Nature reviews. Drug discovery · 2021Review
- Design Considerations for Macroencapsulation Devices for Stem Cell Derived Islets for the Treatment of Type 1 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Review
- Harnessing Proliferation for the Expansion of Stem Cell-Derived Pancreatic Cells: Advantages and Limitations.Frontiers in endocrinology · 2021Review
- Small Molecule-Induced Pancreatic β-Like Cell Development: Mechanistic Approaches and Available Strategies.International journal of molecular sciences · 2020Review
- A hydrogel platform for in vitro three dimensional assembly of human stem cell-derived islet cells and endothelial cells.Acta biomaterialia · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisEndothelial cells (ECs) play an essential role in pancreatic organogenesis. We hypothesise that effective in vitro interactions between human microvascular endothelial cells (HMECs) and human pluripotent stem cells (hPSCs) results in the generation of functional pancreatic beta cells.
methodsEmbryoid bodies (EBs) derived from hPSCs were cultured alone (controls) or with ECs in collagen gels. Subsequently, cells were analysed for pancreatic beta cell markers, and then isolated and expanded. Insulin secretion in response to glucose was evaluated in vitro by static and dynamic (perifusion) assays, and in vivo by EB transplantation into immunodeficient mice.
resultsCo-cultured EBs had a higher expression of mature beta cells markers and enhanced insulin secretion in vitro, compared with controls. In mice, transplanted EBs had higher levels of human C-peptide secretion with a significant reduction in hyperglycaemia after the selective destruction of native pancreatic beta cells. In addition, there was significant in vitro upregulation of bone morphogenetic proteins 2 and 4 (BMP-2, 4) in co-cultured cells, compared with controls. CONCLUSIONS/
interpretationECs provide essential signalling in vitro, such as activation of the BMP pathway, for derivation of functional insulin-producing beta cells from hPSCs.
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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.