ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
IFN-γ and TNF-α Pre-licensing Protects Mesenchymal Stromal Cells from the Pro-inflammatory Effects of Palmitate.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 61 citations in OpenAlex.
- Reciprocal Macrophage-MSC Crosstalk Drives Immunomodulatory and Regenerative Phenotypes in a Mineralized Collagen Scaffold.Journal of biomedical materials research. Part A · 2026Article
- The PPARβ/Delta-Induced Mesenchymal Stromal Cell Secretome Has Cytoprotective Effects via ANGPTL4 in a Pre-Clinical Model of Acute Lung Inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Reciprocal macrophage-MSC crosstalk drives immunomodulatory and regenerative phenotypes in a mineralized collagen scaffold.bioRxiv : the preprint server for biology · 2026Article
- Quantitative evaluation of mesenchymal stromal cell immunomodulatory potency and cost-effectiveness of cytokine licensing for translational application.Journal of translational medicine · 2026Article
- Harnessing MSCs plasticity: mechanisms and determinants of bidirectional immune regulation in stem-cell-based immunotherapy.Stem cell research & therapy · 2026Review
- Mesenchymal stromal cells induce neutrophil aggregation and extracellular vesicle storms for systemic lupus erythematosus.Signal transduction and targeted therapy · 2025Article
- Palmitate enhances MSC immunomodulation of human macrophages via the ceramide/CCL2 axis in vitro.Stem cell research & therapy · 2025Article
- Increasing robustness ofRegenerative therapy · 2025Article
- The VEGF-Mediated Cytoprotective Ability of MIF-Licensed Mesenchymal Stromal Cells in House Dust Mite-Induced Epithelial Damage.European journal of immunology · 2025Article
- Immunomodulatory Mechanisms and Therapeutic Potential of Mesenchymal Stem Cells.Stem cell reviews and reports · 2023Review
- The critical role of apoptosis in mesenchymal stromal cell therapeutics and implications in homeostasis and normal tissue repair.Cellular & molecular immunology · 2023Review
- Dynamics of Ex Vivo Mesenchymal Stromal Cell Potency under Continuous Perfusion.International journal of molecular sciences · 2023Article
- Untargeted mass spectrometry-based metabolomics approach unveils biochemical changes in compound probiotic fermented milk during fermentation.NPJ science of food · 2023Article
- Pretreated Mesenchymal Stem Cells and Their Secretome: Enhanced Immunotherapeutic Strategies.International journal of molecular sciences · 2023Review
- The role of TNF-α in the fate regulation and functional reprogramming of mesenchymal stem cells in an inflammatory microenvironment.Frontiers in immunology · 2023Review
- Overexpression of NDST1 Attenuates Fibrotic Response in Murine Adipose-Derived Stem Cells.Stem cells and development · 2022Article
- Chemokine Assay Matrix Defines the Potency of Human Bone Marrow Mesenchymal Stromal Cells.Stem cells translational medicine · 2022Article
- Injectable Peptide Hydrogel Encapsulation of Mesenchymal Stem Cells Improved Viability, Stemness, Anti-Inflammatory Effects, and Early Stage Wound Healing.Biomolecules · 2022Article
- Immunomodulatory Mechanisms of Mesenchymal Stem Cells and Their Potential Clinical Applications.International journal of molecular sciences · 2022Review
- Interferon-γ enhances the immunosuppressive ability of canine bone marrow-derived mesenchymal stem cells by activating the TLR3-dependent IDO/kynurenine pathway.Molecular biology reports · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The use of mesenchymal stromal cell (MSC) therapy for the treatment of type 2 diabetes (T2D) and T2D complications is promising; however, the investigation of MSC function in the setting of T2D has not been thoroughly explored. In our current study, we investigated the phenotype and function of MSCs in a simulated in vitro T2D environment. We show that palmitate, but not glucose, exposure impairs MSC metabolic activity with moderate increases in apoptosis, while drastically affecting proliferation and morphology. In co-culture with peripheral blood mononuclear cells (PBMCs), we found that MSCs not only lose their normal suppressive ability in high levels of palmitate, but actively support and enhance inflammation, resulting in elevated PBMC proliferation and pro-inflammatory cytokine release. The pro-inflammatory effect of MSCs in palmitate was partially reversed via palmitate removal and fully reversed through pre-licensing MSCs with interferon-gamma and tumor necrosis factor alpha. Thus, palmitate, a specific metabolic factor enriched within the T2D environment, is a potent modulator of MSC immunosuppressive function, which may in part explain the depressed potency observed in MSCs isolated from T2D patients. Importantly, we have also identified a robust and durable pre-licensing regimen that protects MSC immunosuppressive function in the setting of T2D.
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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.