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Stem cells and development2014; 23(11); 1258-1265; doi: 10.1089/scd.2013.0537

Equine mesenchymal stem cells inhibit T cell proliferation through different mechanisms depending on tissue source.

Abstract: Mesenchymal stem cells (MSCs) are used in both human clinical trials and veterinary medicine for the treatment of inflammatory and immune-mediated diseases. MSCs modulate inflammation by decreasing the cells and products of the inflammatory response. Stimulated equine MSCs from bone marrow (BM), adipose tissue (AT), cord blood (CB), and umbilical cord tissue (CT) inhibit lymphocyte proliferation and decrease inflammatory cytokine production. We hypothesized that equine MSCs inhibit T cell proliferation through secreted mediators and that MSCs from different tissue sources decrease T cell proliferation through different mechanisms. To test our hypotheses, we inhibited interleukin-6 (IL-6), nitric oxide (NO), and prostaglandin E2 (PGE2) to determine their impact on stimulated T cell proliferation. We also determined how equine MSCs modulate lymphocyte proliferation either via cell cycle arrest or apoptosis. Inhibition of IL-6 or NO did not reverse the immunomodulatory effect of MSCs on activated T cells. In contrast, inhibition of PGE2 restored T cell proliferation, restored the secretion of tumor necrosis factor-α and interferon-γ, and increased IL-10 levels. MSCs from solid-tissue-derived sources, AT and CT, inhibited T cell proliferation through induction of lymphocyte apoptosis while blood-derived MSCs, BM and CB, induced lymphocyte cell cycle arrest. Equine MSCs from different tissue sources modulated immune cell function by both overlapping and unique mechanisms. MSC tissue source may determine immunomodulatory properties of MSCs and may have very practical implications for MSC selection in the application of MSC therapy.
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Publication Date: 2014-03-04 PubMed ID: 24438346DOI: 10.1089/scd.2013.0537Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the impact of Mesenchymal stem cells (MSCs) from different tissue sources on T cell proliferation. The study shows that these stem cells intefere with T cell growth through various mechanisms depending on their tissue source.

Overview of the Research

  • The research revolves around Mesenchymal stem cells (MSCs) and their role in modulating inflammation in both human and veterinary diseases.
  • Mesenchymal stem cells’ origins can be traced back to different sources including bone marrow, adipose tissue, cord blood and umbilical cord tissue.
  • The objective of the research was to draw a clearer understanding of how MSCs impact the proliferation of T cells, which are crucial for the immune response in the body.
  • Researchers also ventured to study how MSCs taken from different origins impact T cell proliferation mechanisms.

Methodology and Findings

  • To validate the hypotheses, the researchers inhibited interleukin-6 (IL-6), nitric oxide (NO), and prostaglandin E2 (PGE2) to see their effects on T cell proliferation.
  • It was found that the inhibition of IL-6 or NO did not reverse the effect of MSC’s on activated T cells. In contrast, PGE2 inhibition aided in restoring the T cell proliferation.
  • The research also investigated how MSCs work to modulate lymphocyte proliferation—whether through cell cycle arrest or apoptosis.
  • Results showed that MSCs obtained from solid tissues (adipose tissue and umbilical cord tissue) inhibited T cell growth through inducing lymphocyte apoptosis, while MSCs derived from blood (bone marrow and cord blood) caused a halt or delay in the cell cycle of lymphocytes.

Conclusions and Implications

  • The research concludes that equine MSCs obtained from different tissue sources interfere with immune cell function through both overlapping and distinct mechanisms.
  • This discovery that MSCs’ tissue source might determine their immunomodulatory properties has profound implications for choosing suitable MSCs for MSC therapy applications.
  • The tissue source of the MSCs might influence the therapeutic effect and success rate of MSC therapy. Thus, choosing the right MSC source is crucial to leverage its healing properties effectively.

Cite This Article

APA
Carrade Holt DD, Wood JA, Granick JL, Walker NJ, Clark KC, Borjesson DL. (2014). Equine mesenchymal stem cells inhibit T cell proliferation through different mechanisms depending on tissue source. Stem Cells Dev, 23(11), 1258-1265. https://doi.org/10.1089/scd.2013.0537

Publication

Stem cells and development
ISSN: 1557-8534
NlmUniqueID: 101197107
Country: United States
Language: English
Volume: 23
Issue: 11
Pages: 1258-1265

Researcher Affiliations

Carrade Holt, Danielle D
  • 1 Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California , Davis, California.
Wood, Joshua A
    Granick, Jennifer L
      Walker, Naomi J
        Clark, Kaitlin C
          Borjesson, Dori L

            MeSH Terms

            • Adipose Tissue / cytology
            • Adipose Tissue / physiology
            • Animals
            • Bone Marrow Cells / cytology
            • Bone Marrow Cells / physiology
            • Cell Proliferation / drug effects
            • Cell Separation / methods
            • Coculture Techniques
            • Fetal Blood / cytology
            • Fetal Blood / physiology
            • Horses
            • Interleukin-6 / metabolism
            • Interleukin-6 / pharmacology
            • Mesenchymal Stem Cells / cytology
            • Mesenchymal Stem Cells / physiology
            • Nitric Oxide / metabolism
            • Nitric Oxide / pharmacology
            • Signal Transduction
            • T-Lymphocytes / cytology
            • T-Lymphocytes / drug effects
            • T-Lymphocytes / physiology

            Citations

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