ArticleStem cell research & therapy2019
Adult and iPS-derived non-parenchymal cells regulate liver organoid development through differential modulation of Wnt and TGF-β.
Article in Stem cell research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- Construction of liver organoid models by hepatobiliary differentiation from human induced pluripotent stem cells: state of the art, challenges and improving strategies.Stem cell research & therapy · 2026Review
- Human Liver Organoids as an Experimental Tool to Investigate Lipocalin-2 in Hepatic Inflammation.Cells · 2026Article
- Hypoxia and Multilineage Communication in 3D Organoids for Human Disease Modeling.Biomimetics (Basel, Switzerland) · 2025Review
- Potential Use of Organoids in Regenerative Medicine.Tissue engineering and regenerative medicine · 2024Review
- Using Liver Organoids as Models to Study the Pathobiology of Rare Liver Diseases.Biomedicines · 2024Review
- iPSC-derived cells for whole liver bioengineering.Frontiers in bioengineering and biotechnology · 2024Review
- A human liver organoid screening platform for DILI risk prediction.Journal of hepatology · 2023Article
- Review
- Generation of multilineage liver organoids with luminal vasculature and bile ducts from human pluripotent stem cells via modulation of Notch signaling.Stem cell research & therapy · 2023Article
- A Review of Stem Cell Technology Targeting Hepatocyte Growth as an Alternative to Organ Transplantation.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Organ Chips and Visualization of Biological Systems.Advances in experimental medicine and biology · 2023Article
- Leveraging interacting signaling pathways to robustly improve the quality and yield of human pluripotent stem cell-derived hepatoblasts and hepatocytes.Stem cell reports · 2022Article
- Updated perspectives on vascular cell specification and pluripotent stem cell-derived vascular organoids for studying vasculopathies.Cardiovascular research · 2022Review
- Applied Hepatic Bioengineering: Modeling the Human Liver Using Organoid and Liver-on-a-Chip Technologies.Frontiers in bioengineering and biotechnology · 2022Review
- High-throughput bioengineering of homogenous and functional human-induced pluripotent stem cells-derived liver organoidsFrontiers in bioengineering and biotechnology · 2022Article
- Human Pluripotent Stem Cell-Derived Hepatocyte-Like Cells and Organoids for Liver Disease and Therapy.International journal of molecular sciences · 2021Review
- Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Advancements in stem cell-derived hepatocyte-like cell models for hepatotoxicity testing.Stem cell research & therapy · 2021Review
- Challenges for the Applications of Human Pluripotent Stem Cell-Derived Liver Organoids.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLiver organoid technology holds great promises to be used in large-scale population-based drug screening and in future regenerative medicine strategies. Recently, some studies reported robust protocols for generating isogenic liver organoids using liver parenchymal and non-parenchymal cells derived from induced pluripotent stem cells (iPS) or using isogenic adult primary non-parenchymal cells. However, the use of whole iPS-derived cells could represent great challenges for a translational perspective.
methodsHere, we evaluated the influence of isogenic versus heterogenic non-parenchymal cells, using iPS-derived or adult primary cell lines, in the liver organoid development. We tested four groups comprised of all different combinations of non-parenchymal cells for the liver functionality in vitro. Gene expression and protein secretion of important hepatic function markers were evaluated. Additionally, liver development-associated signaling pathways were tested. Finally, organoid label-free proteomic analysis and non-parenchymal cell secretome were performed in all groups at day 12.
resultsWe show that liver organoids generated using primary mesenchymal stromal cells and iPS-derived endothelial cells expressed and produced significantly more albumin and showed increased expression of CYP1A1, CYP1A2, and TDO2 while presented reduced TGF-β and Wnt signaling activity. Proteomics analysis revealed that major shifts in protein expression induced by this specific combination of non-parenchymal cells are related to integrin profile and TGF-β/Wnt signaling activity.
conclusionAiming the translation of this technology bench-to-bedside, this work highlights the role of important developmental pathways that are modulated by non-parenchymal cells enhancing the liver organoid maturation.
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Registered trials
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