ArticlePloS one2018
Microenvironmental cues enhance mesenchymal stem cell-mediated immunomodulation and regulatory T-cell expansion.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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.
The trial behind it
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Who cites it
54 citing papers in PubMed, 89 citations in OpenAlex.
- Cord-Derived Stem Cells for Pediatric Autism Spectrum Disorder: Biological Rationale and Source-Specific Trial Design.International journal of molecular sciences · 2026Review
- Enhancing islet transplantation outcomes in T1DM: The promise of mesenchymal stem cells and exosomes.International journal of pharmaceutics: X · 2026Review
- Harnessing MSCs plasticity: mechanisms and determinants of bidirectional immune regulation in stem-cell-based immunotherapy.Stem cell research & therapy · 2026Review
- Article
- Mesenchymal stem cells in sepsis-induced organ dysfunction: mechanisms and therapeutic potential.Stem cell research & therapy · 2025Review
- Indoleamine-2,3-dioxygenase: An important controller in maintaining mesenchymal stem cell-mediated immunomodulatory homeostasis.Acta pharmaceutica Sinica. B · 2025Review
- Concurrent hypoxia and apoptosis imparts immune programming potential in mesenchymal stem cells: Lesson from acute graft-versus-host-disease model.Stem cell research & therapy · 2024Article
- High throughput screening of mesenchymal stromal cell morphological response to inflammatory signals for bioreactor-based manufacturing of extracellular vesicles that modulate microglia.Bioactive materials · 2024Article
- Treatment of cytokine release syndrome-induced vascular endothelial injury using mesenchymal stem cells.Molecular and cellular biochemistry · 2024Review
- Enhanced potent immunosuppression of intracellular adipose tissue-derived stem cell extract by priming with three-dimensional spheroid formation.Scientific reports · 2024Article
- Impacts of priming on distinct immunosuppressive mechanisms of mesenchymal stromal cells under translationally relevant conditions.Stem cell research & therapy · 2024Article
- Stem cell therapies: a new era in the treatment of multiple sclerosis.Frontiers in neurology · 2024Review
- Spheroid trilineage differentiation model of primary mesenchymal stem/stromal cells under hypoxia and serum-free culture conditions.Frontiers in bioengineering and biotechnology · 2024Article
- High throughput screening of mesenchymal stromal cell morphological response to inflammatory signals for bioreactor-based manufacturing of extracellular vesicles that modulate microglia.bioRxiv : the preprint server for biology · 2023Article
- Immunomodulatory Mechanisms and Therapeutic Potential of Mesenchymal Stem Cells.Stem cell reviews and reports · 2023Review
- Immunomodulatory properties of mesenchymal stromal/stem cells: The link with metabolism.Journal of advanced research · 2023Review
- Pretreated Mesenchymal Stem Cells and Their Secretome: Enhanced Immunotherapeutic Strategies.International journal of molecular sciences · 2023Review
- Macrophages-bone marrow mesenchymal stem cells crosstalk in bone healing.Frontiers in cell and developmental biology · 2023Review
- Mesenchymal stem cell-derived exosomes can alleviate GVHD and preserve the GVL effect in allogeneic stem cell transplantation animal models.Frontiers in immunology · 2023Article
- The Evolving Landscape of Potency Assays.Advances in experimental medicine and biology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Mesenchymal stem cells (MSCs) are known to both have powerful immunosuppressive properties and promote allograft tolerance. Determining the environmental oxygen tension and inflammatory conditions under which MSCs are optimally primed for this immunosuppressive function is essential to their utilization in promoting graft tolerance. Of particular interest is the mechanisms governing the interaction between MSCs and regulatory T cells (Tregs), which is relatively unknown. We performed our experiments utilizing rat bone marrow derived MSCs. We observed that priming MSCs in hypoxia promotes maintenance of stem-like characteristics, with greater expression of typical MSC cell-surface markers, increased proliferation, and maintenance of differentiation potential. Addition of autologous MSCs to CD4+/allogeneic endothelial cell (EC) co-culture increases regulatory T cell (Treg) proliferation, which is further enhanced when MSCs are primed in hypoxia. Furthermore, MSC-mediated Treg expansion does not require direct cell-cell contact. The expression of indolamine 2,3-dioxygenase, a mediator of MSC immunomodulation, increases when MSCs are primed in hypoxia, and inhibition of IDO significantly decreases the expansion of Tregs. Priming with inflammatory cytokines IFNγ and TNFα increases also expression of markers associated with MSC immunomodulatory function, but decreases MSC proliferation. The expression of IDO also increases when MSCs are primed with inflammatory cytokines. However, there is no increase in Treg expansion when MSCs are primed with IFNγ, suggesting an alternate mechanism for inflammatory-stimulated MSC immunomodulation. Overall, these results suggest that MSCs primed in hypoxia or inflammatory conditions are optimally primed for immunosuppressive function. These results provide a clearer picture of how to enhance MSC immunomodulation for clinical use.
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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.