ArticleStem cell reviews and reports2019
Islet-Like Structures Generated In Vitro from Adult Human Liver Stem Cells Revert Hyperglycemia in Diabetic SCID Mice.
Article in Stem cell reviews and reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Scaffold-free endocrine tissue engineering: role of islet organization and implications in type 1 diabetes.BMC endocrine disorders · 2025Review
- Large-Scale Expansion of Human Liver Stem Cells Using Two Different Bioreactor Systems.Bioengineering (Basel, Switzerland) · 2024Article
- Traditional and emerging strategies using hepatocytes for pancreatic regenerative medicine.Journal of diabetes · 2024Review
- Challenges of CRISPR/Cas-Based Cell Therapy for Type 1 Diabetes: How Not to Engineer a "Trojan Horse".International journal of molecular sciences · 2023Review
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- Insulin-producing cell clusters derived from human gingival mesenchymal stem cells as a model for diabetes research.Molecular biology reports · 2022Article
- Resistance of Human Liver Mesenchymal Stem Cells to FAS-Induced Cell Death.Current issues in molecular biology · 2022Article
- Making human pancreatic islet organoids: Progresses on the cell origins, biomaterials and three-dimensional technologies.Theranostics · 2022Review
- In Vitro Disease Models of the Endocrine Pancreas.Biomedicines · 2021Review
- Differentiation of Cells Isolated from Afterbirth Tissues into Hepatocyte-Like Cells and Their Potential Clinical Application in Liver Regeneration.Stem cell reviews and reports · 2021Review
- Human Liver Stem Cells: A Liver-Derived Mesenchymal Stromal Cell-Like Population With Pro-regenerative Properties.Frontiers in cell and developmental biology · 2021Review
- Fibroblast growth factor-4 maintains cellular viability while enhancing osteogenic differentiation of stem cell spheroids in part by regulating RUNX2 and BGLAP expression.Experimental and therapeutic medicine · 2020Article
- Current progress in stem cell therapy for type 1 diabetes mellitus.Stem cell research & therapy · 2020Review
- Article
- HLSC-Derived Extracellular Vesicles Attenuate Liver Fibrosis and Inflammation in a Murine Model of Non-alcoholic Steatohepatitis.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Intrahepatic Administration of Human Liver Stem Cells in Infants with Inherited Neonatal-Onset Hyperammonemia: A Phase I Study.Stem cell reviews and reports · 2020Article
- Commentary: Insulin-Producing Organoids Engineered From Islet and Amniotic Epithelial Cells to Treat Diabetes.Frontiers in endocrinology · 2020Article
- Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models.Frontiers in bioengineering and biotechnology · 2020Review
- Human Liver-Derived Stem Cells Improve Fibrosis and Inflammation Associated with Nonalcoholic Steatohepatitis.Stem cells international · 2019Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A potential therapeutic strategy for diabetes is the transplantation of induced-insulin secreting cells. Based on the common embryonic origin of liver and pancreas, we studied the potential of adult human liver stem-like cells (HLSC) to generate in vitro insulin-producing 3D spheroid structures (HLSC-ILS). HLSC-ILS were generated by a one-step protocol based on charge dependent aggregation of HLSC induced by protamine. 3D aggregation promoted the spontaneous differentiation into cells expressing insulin and several key markers of pancreatic β cells. HLSC-ILS showed endocrine granules similar to those seen in human β cells. In static and dynamic in vitro conditions, such structures produced C-peptide after stimulation with high glucose. HLSC-ILS significantly reduced hyperglycemia and restored a normo-glycemic profile when implanted in streptozotocin-diabetic SCID mice. Diabetic mice expressed human C-peptide and very low or undetectable levels of murine C-peptide. Hyperglycemia and a diabetic profile were restored after HLSC-ISL explant. The gene expression profile of in vitro generated HLSC-ILS showed a differentiation from HLSC profile and an endocrine commitment with the enhanced expression of several markers of β cell differentiation. The comparative analysis of gene expression profiles after 2 and 4 weeks of in vivo implantation showed a further β-cell differentiation, with a genetic profile still immature but closer to that of human islets. In conclusion, protamine-induced spheroid aggregation of HLSC triggers a spontaneous differentiation to an endocrine phenotype. Although the in vitro differentiated HLSC-ILS were immature, they responded to high glucose with insulin secretion and in vivo reversed hyperglycemia in diabetic SCID mice.
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