ArticleStem cell research & therapy2015
Hypoxic preconditioning potentiates the trophic effects of mesenchymal stem cells on co-cultured human primary hepatocytes.
Article in Stem cell research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 52 citations in OpenAlex.
- TGF-β Receptor Inhibitor SB431542 Enhanced the Sensitivity of Gastric Cancer to 5-Fluorouracil: New Combined Targeted Therapy.International journal of molecular sciences · 2025Article
- The dual role of mesenchymal stem cells in apoptosis regulation.Cell death & disease · 2024Review
- The Crosstalk between Mesenchymal Stromal/Stem Cells and Hepatocytes in Homeostasis and under Stress.International journal of molecular sciences · 2023Review
- ABCB5Stem cell research & therapy · 2023Article
- Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells and Their Contribution to Angiogenic Processes in Tissue Regeneration.International journal of molecular sciences · 2022Review
- Effectiveness of mesenchymal stem cells cultured under hypoxia to increase the fertility rate in rats (Veterinary world · 2021Article
- Programmed cell death in stem cell-based therapy: Mechanisms and clinical applications.World journal of stem cells · 2021Review
- Discrepancies on the Role of Oxygen Gradient and Culture Condition on Mesenchymal Stem Cell Fate.Advanced healthcare materials · 2021Review
- Application of adipose-derived stem cells in photoaging: basic science and literature review.Stem cell research & therapy · 2020Review
- Co-encapsulation of HNF4α overexpressing UMSCs and human primary hepatocytes ameliorates mouse acute liver failure.Stem cell research & therapy · 2020Article
- The emerging antioxidant paradigm of mesenchymal stem cell therapy.Stem cells translational medicine · 2020Review
- Regulation of Angiogenesis Discriminates Tissue Resident MSCs from Effective and Defective Osteogenic Environments.Journal of clinical medicine · 2020Article
- Progressive hypoxia-on-a-chip: An in vitro oxygen gradient model for capturing the effects of hypoxia on primary hepatocytes in health and disease.Biotechnology and bioengineering · 2020Article
- Hypoxia-Preconditioned Wharton's Jelly-Derived Mesenchymal Stem Cells Mitigate Stress-Induced Apoptosis and Ameliorate Human Islet Survival and Function in Direct Contact Coculture System.Stem cells international · 2020Article
- FGF-17 from Hypoxic Human Wharton's Jelly-Derived Mesenchymal Stem Cells Is Responsible for Maintenance of Cell Proliferation at Late Passages.International journal of stem cells · 2019Article
- Comparison of biotechnological culture of hypoxia-conditioned rat mesenchymal stem cells with conventionalVeterinary world · 2019Article
- NUPR1 acts as a pro-survival factor in human bone marrow-derived mesenchymal stem cells and is induced by the hypoxia mimetic reagent deferoxamine.Journal of clinical biochemistry and nutrition · 2019Article
- Physioxia: a more effective approach for culturing human adipose-derived stem cells for cell transplantation.Stem cell research & therapy · 2018Article
- A New High Throughput Screening Platform for Cell Encapsulation in Alginate Hydrogel Shows Improved Hepatocyte Functions by Mesenchymal Stromal Cells Co-encapsulation.Frontiers in medicine · 2018Article
- Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocyte Viability and Albumin Secretion.Journal of immunology research · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionMesenchymal stem/stromal cells (MSCs) improve the metabolic function of co-cultured hepatocytes. The present study aimed to further enhance the trophic effects of co-culture with hepatocytes using hypoxic preconditioning (HPc) of the MSCs and also to investigate the underlying molecular mechanisms involved.
methodsHuman adipose tissue-derived MSCs were subjected to hypoxia (2 % O2; HPc) or normoxia (20 % O2) for 24 h and then co-cultured with isolated human hepatocytes. Assays of metabolic function and apoptosis were performed to investigate the hepatotrophic and anti-apoptotic effects of co-culture. Indirect co-cultures and co-culture with MSC-conditioned medium investigated the role of paracrine factors in the hepatotrophic effects of co-culture. Reactive oxygen species (ROS) activity was antagonised with N-acetylcysteine to investigate whether HPc potentiated the effects of MSCs by intracellular ROS-dependent mechanisms. Tumour necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, and extracellular collagen production was determined and CASP9 and BAX/BCL-2 signalling pathways analysed to investigate the role of soluble factors, extracellular matrix deposition, and apoptosis-associated gene signalling in the effects of co-culture.
resultsHPc potentiated the hepatotrophic and anti-apoptotic effects of co-culture by ROS-dependent mechanisms. There was increased MSC TGF-β1 production, and enhanced MSC deposition of extracellular collagen, with reduced synthesis of TNF-α, as well as a downregulation of the expression of pro-apoptotic CASP9, BAX, BID and BLK genes and upregulated expression of anti-apoptotic BCL-2 in hepatocytes.
conclusionsHPc potentiated the trophic and anti-apoptotic effects of MSCs on hepatocytes via mechanisms including intracellular ROS, autocrine TGF-β, extracellular collagen and caspase and BAX/BCL-2 signalling pathways.
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