ArticleStem cell research & therapy2023
ADSC secretome constrains NK cell activity by attenuating IL-2-mediated JAK-STAT and AKT signaling pathway via upregulation of CIS and DUSP4.
Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 14 citations in OpenAlex.
- Review
- Enhancement of NK cell activity via DNA-sensing inhibition by Poxin transgene.Journal of advanced research · 2026Article
- In vitro assays for investigating the immunomodulatory properties of human mesenchymal stromal cells.Stem cell research & therapy · 2026Review
- A framework integrating multiscale in silico modeling and experimental data predicts CAR-NK cell cytotoxicity across target cell types.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Advancing fat graft survival: from adipose-derived stem cell mechanisms to next-generation regenerative strategies.Frontiers in cell and developmental biology · 2026Review
- Review
- A biofabricated 3D cancer-stroma tumor microenvironment model.Biofabrication · 2025Article
- Emerging insights into mesenchymal stem cells and exosome-based therapies for liver injury.Biomolecules & biomedicine · 2025Review
- Research progress on the mechanism underlying the application of mesenchymal stem cells in the treatment of male infertility.Frontiers in endocrinology · 2025Review
- Mesenchymal stem cell therapy for liver transplantation: clinical progress and immunomodulatory properties.Stem cell research & therapy · 2024Review
- Distinct adaptive immune receptor feature of adipose-derived mesenchymal stem cells (AD-MSCs) treatment of psoriasis.Archives of dermatological research · 2024Article
- Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments.International journal of molecular sciences · 2024Review
- Recent advances in the role of mesenchymal stem cells as modulators in autoinflammatory diseases.Frontiers in immunology · 2024Review
- The therapeutic potential of exosomes in immunotherapy.Frontiers in immunology · 2024Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMesenchymal stem cells (MSCs) have immunomodulatory properties and therapeutic effects on autoimmune diseases through their secreted factors, referred to as the secretome. However, the specific key factors of the MSC secretome and their mechanisms of action in immune cells have not been fully determined. Most in vitro experiments are being performed using immune cells, but experiments using natural killer (NK) cells have been neglected, and a few studies using NK cells have shown discrepancies in results. NK cells are crucial elements of the immune system, and adjustment of their activity is essential for controlling various pathological conditions. The aim of this study was to elucidate the role of the adipose tissue-derived stem cell (ADSC) secretome on NK cell activity.
methodsTo obtain the ADSC secretome, we cultured ADSCs in medium and concentrated the culture medium using tangential flow filtration (TFF) capsules. We assessed NK cell viability and proliferation using CCK-8 and CFSE assays, respectively. We analyzed the effects of the ADSC secretome on NK cell activity and pathway-related proteins using a combination of flow cytometry, ELISA, cytotoxicity assay, CD107a assay, western blotting, and quantitative real-time PCR. To identify the composition of the ADSC secretome, we performed LC-MS/MS profiling and bioinformatics analysis. To elucidate the molecular mechanisms involved, we used mRNA sequencing to profile the transcriptional expression of human blood NK cells.
resultsThe ADSC secretome was found to restrict IL-2-mediated effector function of NK cells while maintaining proliferative potency. This effect was achieved through the upregulation of the inhibitory receptor CD96, as well as downregulation of activating receptors and IL-2 receptor subunits IL-2Rα and IL-2Rγ. These changes were associated with attenuated JAK-STAT and AKT pathways in NK cells, which were achieved through the upregulation of cytokine-inducible SH2-containing protein (CIS, encoded by Cish) and dual specificity protein phosphatase 4 (DUSP4). Furthermore, proteomic analysis revealed twelve novel candidates associated with the immunomodulatory effects of MSCs.
conclusionsOur findings reveal a detailed cellular outcome and regulatory mechanism of NK cell activity by the ADSC secretome and suggest a therapeutic tool for treating NK-mediated inflammatory and autoimmune diseases using the MSC secretome.
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