ArticleStem cells (Dayton, Ohio)2015
PI3kα and STAT1 Interplay Regulates Human Mesenchymal Stem Cell Immune Polarization.
Article in Stem cells (Dayton, Ohio), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 70 citations in OpenAlex.
- Applications and prospects of the immunomodulatory and regenerative capabilities of gingival mesenchymal stem cells for chronic inflammation treatment.Molecular biology reports · 2026Review
- Low dose IFNγ remodels enhancer landscape to potentiate mesenchymal stromal cell activation.Stem cell research & therapy · 2025Article
- Engineered MSC Aggregates with E/N-Cadherin and IL-6 Preconditioning for the Treatment of Systemic Sclerosis.Advanced healthcare materials · 2025Article
- Indoleamine-2,3-dioxygenase: An important controller in maintaining mesenchymal stem cell-mediated immunomodulatory homeostasis.Acta pharmaceutica Sinica. B · 2025Review
- Galectin-3 Release in the Bone Marrow Microenvironment Promotes Drug Resistance and Relapse in Acute Myeloid Leukemia.Life (Basel, Switzerland) · 2025Review
- Proteomic analysis of human Wharton's jelly mesenchymal stem/stromal cells and human amniotic epithelial stem cells: a comparison of therapeutic potential.Scientific reports · 2024Article
- Interferon-gamma Treatment of Human Umbilical Cord Mesenchymal Stem Cells can Significantly Reduce Damage Associated with Diabetic Peripheral Neuropathy in Mice.Current stem cell research & therapy · 2024Article
- Mesenchymal Stromal Cells: New Generation Treatment of Inflammatory Bowel Disease.Journal of inflammation research · 2024Review
- Stem Cell Therapy in Inflammatory Bowel Disease: A Review of Achievements and Challenges.Journal of inflammation research · 2023Review
- Regulatory T-Cell Enhancement, Expression of Adhesion Molecules, and Production of Anti-Inflammatory Factors Are Differentially Modulated by Spheroid-Cultured Mesenchymal Stem Cells.International journal of molecular sciences · 2022Article
- TNFα and IFNγ rapidly activate PI3K-AKT signaling to drive glycolysis that confers mesenchymal stem cells enhanced anti-inflammatory property.Stem cell research & therapy · 2022Article
- Cross talk between glucose metabolism and immunosuppression in IFN-γ-primed mesenchymal stem cells.Life science alliance · 2022Article
- Stem Cell-Based Therapies for Inflammatory Bowel Disease.International journal of molecular sciences · 2022Review
- Review
- Equilibrium among Inflammatory Factors Determines Human MSC-Mediated Immunosuppressive Effect.Cells · 2022Article
- The secretion profile of mesenchymal stem cells and potential applications in treating human diseases.Signal transduction and targeted therapy · 2022Review
- Bone Mesenchymal Stem Cell-Derived Exosome-Enclosed miR-181a Induces CD4Journal of oncology · 2022Article
- Strategies for the induction of anti-inflammatory mesenchymal stem cells and their application in the treatment of immune-related nephropathy.Frontiers in medicine · 2022Review
- Inflammation, a common mechanism in frailty and COVID-19, and stem cells as a therapeutic approach.Stem cells translational medicine · 2021Review
- IFN-γ and PPARδ influence the efficacy and retention of multipotent adult progenitor cells in graft vs host disease.Stem cells translational medicine · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
The immunomodulatory capacity of mesenchymal stem cells (MSCs) is critical for their use in therapeutic applications. MSC response to specific inflammatory cues allows them to switch between a proinflammatory (MSC1) or anti-inflammatory (MSC2) phenotype. Regulatory mechanisms controlling this switch remain to be defined. One characteristic feature of MSC2 is their ability to respond to IFNγ with induction of indoleamine 2,3-dioxygenase (IDO), representing the key immunoregulatory molecule released by human MSC. Here, we show that STAT1 and PI3Kα pathways interplay regulates IFNγ-induced IDO production in MSC. Chemical phosphoinositide 3-kinase (PI3K) pan-inhibition, PI3Kα-specific inhibition or shRNA knockdown diminished IFNγ-induced IDO production. This effect involved PI3Kα-mediated upregulation of STAT1 protein levels and phosphorylation at Ser727. Overexpression of STAT1 or of a constitutively active PI3Kα mutant failed to induce basal IDO production, but shifted MSC into an MSC2-like phenotype by strongly enhancing IDO production in response to IFNγ as compared to controls. STAT1 overexpression strongly enhanced MSC-mediated T-cell suppression. The same effect could be induced using short-term pretreatment of MSC with a chemical inhibitor of the counter player of PI3K, phosphatase and tensin homolog. Finally, downregulation of STAT1 abrogated the immunosuppressive capacity of MSC. Our results for the first time identify critical upstream signals for the induced production of IDO in MSCs that could be manipulated therapeutically to enhance their immunosuppressive phenotype.
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What OpenQuestion holds
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.