ArticleOncotarget2016
Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
What it found
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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.
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Who cites it
93 citing papers in PubMed, 173 citations in OpenAlex.
- Metabolic reprogramming of myeloid cells in cancer: from lactate-NAMPT axis to AI-guided therapeutics.Experimental & molecular medicine · 2026Review
- Reciprocal Macrophage-MSC Crosstalk Drives Immunomodulatory and Regenerative Phenotypes in a Mineralized Collagen Scaffold.Journal of biomedical materials research. Part A · 2026Article
- Reciprocal macrophage-MSC crosstalk drives immunomodulatory and regenerative phenotypes in a mineralized collagen scaffold.bioRxiv : the preprint server for biology · 2026Article
- Lactate: elucidating its indispensable role in human health.Molecular cancer · 2026Review
- Targeting macrophage polarization: mechanisms and potential of mesenchymal stromal/stem cells therapy in acne treatment- a narrative review.Frontiers in immunology · 2026Review
- Immunomodulatory properties of umbilical cord mesenchymal stromal cells in immune disorders: immunoregulatory functions, therapeutic progress, and engineering strategies for enhanced efficacy.Frontiers in immunology · 2026Review
- The Increased Secretion of Lactate Observed in Obesity and Aging Leads to the Generation of Pathogenic B Cells.European journal of immunology · 2026Article
- Macrophage polarisation under immune regulation as a therapeutic target for tendon-bone healing: multifactorial regulation and mechanistic insights.Frontiers in immunology · 2026Review
- Size-dependent immunomodulation by MSC secretome: soluble factors target innate pathways, components larger than 100 kDa regulate T cell proliferation.Stem cell research & therapy · 2025Article
- Crosstalk between macrophages and mesenchymal stem cells shape patterns of osteogenesis and immunomodulation in mineralized collagen scaffolds.Bioactive materials · 2025Article
- Functional impacts of lactylation in Hypoxia‒primed mesenchymal stromal cells.Frontiers in cell and developmental biology · 2025Review
- Serum pyruvate and lactate predict immunotherapy efficacy in advanced gastric cancer: a prospective biomarker study.Frontiers in immunology · 2025Observational
- Multiomics analyses reveal adipose-derived stem cells inhibit the inflammatory response of M1-like macrophages through secreting lactate.Stem cell research & therapy · 2024Article
- Lactic acid: a narrative review of a promoter of the liver cancer microenvironment.Journal of gastrointestinal oncology · 2024Review
- Lactate: a rising star in tumors and inflammation.Frontiers in immunology · 2024Review
- Lactate: an alternative pathway for the immunosuppressive properties of mesenchymal stem/stromal cells.Stem cell research & therapy · 2023Article
- Review
- Therapeutic Efficacy of Mesenchymal Stem/Stromal Cell Small Extracellular Vesicles in Alleviating Arthritic Progression by Restoring Macrophage Balance.Biomolecules · 2023Article
- Insights on the role of L-lactate as a signaling molecule in skin aging.Biogerontology · 2023Review
- Expansion of human bone marrow-derived mesenchymal stromal cells with enhanced immunomodulatory properties.Stem cell research & therapy · 2023Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 4 countries.
Funding
Abstract
Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-macrophage features in terms of morphology, surface markers, migratory properties and antigen presentation capacity. Microarray expression profiling indicates that UC-MSC modify the expression of metabolic-related genes and induce a M2-macrophage expression signature. Importantly, monocyte-derived DC obtained in presence of UC-MSC, polarize naïve allogeneic CD4+ T-cells into Th2 cells. Treatment of UC-MSC with an inhibitor of lactate dehydrogenase strongly decreases lactate concentration in culture supernatant and abrogates the effect on monocyte-to-DC differentiation. Metabolic analysis further revealed that UC-MSC decrease oxidative phosphorylation in differentiating monocytes while strongly increasing the spare respiratory capacity proportional to the amount of secreted lactate. Because both MSC and monocytes are recruited in vivo at the site of tissue damage and inflammation, we propose the local increase of lactate concentration induced by UC-MSC and the consequent enrichment in M2-macrophage generation as a mechanism to achieve immunomodulation.
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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.