ArticleStem cell research & therapy2019
MSC-secreted TGF-β regulates lipopolysaccharide-stimulated macrophage M2-like polarization via the Akt/FoxO1 pathway.
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 208 papers, 3 of them syntheses that pooled it.
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Who cites it
208 citing papers in PubMed, 3 syntheses or guidelines pooled it, 355 citations in OpenAlex.
- Efficacy and safety of mesenchymal stem cell therapies for ischemic stroke: a systematic review and meta-analysis.Stem cells translational medicine · 2024Pooled it
- Advances in the research of the role of macrophage/microglia polarization-mediated inflammatory response in spinal cord injury.Frontiers in immunology · 2022Pooled it
- The safety of MSC therapy over the past 15 years: a meta-analysis.Stem cell research & therapy · 2021Pooled it
- Mitochondrial reprogramming of alveolar macrophages by umbilical cord mesenchymal stem cells restores immune homeostasis inMaterials today. Bio · 2026Article
- NSUN2-Mediated mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- M2 polarization of macrophages: Manipulation of spinal cord injury repair.Neural regeneration research · 2026Article
- Equine mesenchymal stromal cells dual-primed with TGF-β1 and IL-1β or TNF-α improve epithelial healing.Research square · 2026Article
- Bone Marrow-Derived Mesenchymal Stem Cells Alleviate Cutaneous Leishmaniasis by Promoting M2 Macrophage Polarization and Skin Tissue Repair in a Murine Model.Biomolecules · 2026Article
- Mesenchymal stromal cells and neuroinflammation: a multimodal approach to neuroprotection and future therapeutic horizons.Translational neurodegeneration · 2026Review
- β-elemene enhances the efficacy of PD-L1 inhibitor in lung cancer by reprogramming tumor-associated macrophages to M1 phenotype via suppressing FLT1/PI3K/AKT signaling.Cancer immunology, immunotherapy : CII · 2026Article
- Adipose-derived mesenchymal stromal cells promote an exhaustion-associated phenotype in T cells through TIM-3 upregulation independent of PD-1.Discover oncology · 2026Article
- Exosomes derived from TGF-β1-modified mesenchymal stem cells protect septic mice by inducing macrophage M2 polarization.Molecular biology reports · 2026Article
- AnACS omega · 2026Article
- Recent progress in macrophage-mediated tendon injury and healing.Histology and histopathology · 2026Review
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- CAR-engineered cell therapies: current understandings and future perspectives.Molecular biomedicine · 2026Review
- TSG-6 Activated MSC-derived Extracellular Vesicles Present Altered micro-RNA Contents and Ameliorate the Inflammatory Phenotype of Macrophages in Vitro.Inflammation · 2026Article
- Mechanism of ultrasound-guided renal parenchymal injection of MSCs for the treatment of chronic kidney disease: down-regulated SGK1 promotes M2 macrophage polarization.European journal of medical research · 2026Article
- Recent advances and challenges in hydrogel-based delivery of immunomodulatory strategies for diabetic wound healing.Theranostics · 2026Review
- Beyond wound closure: translational opportunities and barriers of mesenchymal stem cells and their extracellular vesicles in burn management.Frontiers in cell and developmental biology · 2026Review
148 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAn uncontrolled inflammatory response is a critical pathophysiological feature of sepsis. Mesenchymal stem cells (MSCs) induce macrophage phenotype polarization and reduce inflammation in sepsis. MSC-secreted transforming growth factor beta (TGF-β) participated in the immune modulatory function of MSCs. However, the underlying mechanism of MSC-secreted TGF-β was not fully elucidated in regulation macrophage M2-like polarization.
methodsThe paracrine effects of MSCs on macrophage polarization were studied using a co-culture protocol with LPS-stimulated RAW264.7 cells/mouse peritoneal macrophages and MSCs. The effect of TGF-β in the co-culture system was blocked by the TGF-β receptor inhibitor. To determine the role of MSC-secreted TGF-β, we used recombinant TGF-β to culture with LPS-stimulated RAW264.7 cells. In addition, we employed antibody microarray analysis to determine the mechanisms of MSC secreted TGF-β on LPS-stimulated RAW264.7 cell/mouse peritoneal macrophage M2-like polarization. Furthermore, we used an Akt inhibitor and a FoxO1 inhibitor to inhibit the Akt/FoxO1 pathway. The nuclear translocation of FoxO1 was detected by Western blot.
resultsMSCs induced LPS-stimulated RAW264.7 cell/mouse peritoneal macrophage polarization towards the M2-like phenotype and significantly reduced pro-inflammatory cytokine levels via paracrine, which was inhibited by TGF-β receptor inhibitor. Furthermore, we found that MSC-secreted TGF-β enhanced the macrophage phagocytic ability. The antibody microarray analysis and Western blot verified that TGF-β treatment activated the Akt/FoxO1 pathway in LPS-stimulated macrophages, TGF-β-induced FoxO1 nuclear translocation and obviously expressed in the cytoplasm, the effects of TGF-β regulatory effects on LPS-stimulated macrophage were inhibited by pre-treatment with Akt inhibitor and FoxO1 inhibitor.
conclusionsTGF-β secreted by MSCs could skew LPS-stimulated macrophage polarization towards the M2-like phenotype, reduce inflammatory reactions, and improve the phagocytic ability via the Akt/FoxO1 pathway, providing potential therapeutic strategies for sepsis.
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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.