ArticleStem cell research & therapy2017
Overexpression of hypoxia-inducible factor 1 alpha improves immunomodulation by dental mesenchymal stem cells.
Article in Stem cell research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 95 citations in OpenAlex.
- RGD-modified alginate enhances viability, metabolic reprogramming, and cytokine secretion profiles in encapsulated mesenchymal stromal cells.Scientific reports · 2026Article
- Essential role of the metabolite α-ketoglutarate in bone tissue and bone-related diseases.Acta biochimica et biophysica Sinica · 2025Review
- Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights.Stem cell research & therapy · 2025Review
- Tissue engineering approaches for dental pulp regeneration: The development of novel bioactive materials using pharmacological epigenetic inhibitors.Bioactive materials · 2024Review
- Mesenchymal Stromal Cells Derived from Dental Tissues: Immunomodulatory Properties and Clinical Potential.International journal of molecular sciences · 2024Review
- Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner.Protein & cell · 2024Article
- Rebuilding the myocardial microenvironment to enhance mesenchymal stem cells-mediated regeneration in ischemic heart disease.Frontiers in bioengineering and biotechnology · 2024Review
- Exploration of altered miRNA expression and function in MSC-derived extracellular vesicles in response to hydatid antigen stimulation.Frontiers in microbiology · 2024Article
- Physiological oxygen conditions enhance the angiogenic properties of extracellular vesicles from human mesenchymal stem cells.Stem cell research & therapy · 2023Article
- Adult Mesenchymal Stem Cells from Oral Cavity and Surrounding Areas: Types and Biomedical Applications.Pharmaceutics · 2023Review
- Pooled evidence from preclinical and clinical studies for stem cell-based therapy in ARDS and COVID-19.Molecular and cellular biochemistry · 2023Review
- MSC based gene delivery methods and strategies improve the therapeutic efficacy of neurological diseases.Bioactive materials · 2023Review
- Immunomodulatory Mechanism and Potential Application of Dental Pulp-Derived Stem Cells in Immune-Mediated Diseases.International journal of molecular sciences · 2023Review
- Harnessing and honing mesenchymal stem/stromal cells for the amelioration of graft-versus-host disease.World journal of stem cells · 2023Review
- HIF-1α-Overexpressing Mesenchymal Stem Cells Attenuate Colitis by Regulating M1-like Macrophages Polarization toward M2-like Macrophages.Biomedicines · 2023Article
- Immunomodulatory properties of mesenchymal stromal/stem cells: The link with metabolism.Journal of advanced research · 2023Review
- Mesenchymal Stem Cells and Their Exocytotic Vesicles.International journal of molecular sciences · 2023Review
- Pretreated Mesenchymal Stem Cells and Their Secretome: Enhanced Immunotherapeutic Strategies.International journal of molecular sciences · 2023Review
- Glycolytic reprogramming in macrophages and MSCs during inflammation.Frontiers in immunology · 2023Article
- Injectable Peptide Hydrogel Encapsulation of Mesenchymal Stem Cells Improved Viability, Stemness, Anti-Inflammatory Effects, and Early Stage Wound Healing.Biomolecules · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman dental mesenchymal stem cells (MSCs) are considered as highly accessible and attractive MSCs for use in regenerative medicine, yet some of their features are not as well characterized as other MSCs. Hypoxia-preconditioning and hypoxia-inducible factor 1 (HIF-1) alpha overexpression significantly improves MSC therapeutics, but the mechanisms involved are not fully understood. In the present study, we characterize immunomodulatory properties of dental MSCs and determine changes in their ability to modulate adaptive and innate immune populations after HIF-1 alpha overexpression.
methodsHuman dental MSCs were stably transduced with green fluorescent protein (GFP-MSCs) or GFP-HIF-1 alpha lentivirus vectors (HIF-MSCs). A hypoxic-like metabolic profile was confirmed by mitochondrial and glycolysis stress test. Capacity of HIF-MSCs to modulate T-cell activation, dendritic cell differentiation, monocyte migration, and polarizations towards macrophages and natural killer (NK) cell lytic activity was assessed by a number of functional assays in co-cultures. The expression of relevant factors were determined by polymerase chain reaction (PCR) analysis and enzyme-linked immunosorbent assay (ELISA).
resultsWhile HIF-1 alpha overexpression did not modify the inhibition of T-cell activation by MSCs, HIF-MSCs impaired dendritic cell differentiation more efficiently. In addition, HIF-MSCs showed a tendency to induce higher attraction of monocytes, which differentiate into suppressor macrophages, and exhibited enhanced resistance to NK cell-mediated lysis, which supports the improved therapeutic capacity of HIF-MSCs. HIF-MSCs also displayed a pro-angiogenic profile characterized by increased expression of CXCL12/SDF1 and CCL5/RANTES and complete loss of CXCL10/IP10 transcription.
conclusionsImmunomodulation and expression of trophic factors by dental MSCs make them perfect candidates for cell therapy. Overexpression of HIF-1 alpha enhances these features and increases their resistance to allogenic NK cell lysis and, hence, their potential in vivo lifespan. Our results further support the use of HIF-1 alpha-expressing dental MSCs for cell therapy in tissue injury and immune disorders.
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