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Stem cell research & therapy2014; 5(4); 90; doi: 10.1186/scrt479

Equine mesenchymal stromal cells and embryo-derived stem cells are immune privileged in vitro.

Abstract: Autologous mesenchymal stem cells (MSCs) are an attractive concept in regenerative medicine, but their mechanism of action remains poorly defined. No immune response is reported after in vivo injection of allogeneic equine MSCs or embryo-derived stem cells (ESCs) into the equine tendon, which may be due to the cells' immune-privileged properties. This study further investigates these properties to determine their potential for clinical application in other tissues. Methods: Mitomycin C-treated MSCs, ESCs, or differentiated ESCs (dESCs) were cultured with allogeneic equine peripheral blood mononuclear cells (PBMCs), and their effect on PBMC proliferation, in the presence or absence of interferon-gamma (IFN-γ) was determined. MSCs and super-antigen (sAg)-stimulated PBMCs were co-cultured directly or indirectly in transwells, and PBMC proliferation examined. Media from MSC culture were harvested and used for PBMC culture; subsequent PBMC proliferation and gene expression were evaluated and media assayed for IFN-γ, tumor necrosis factor alpha (TNF-α), and interleukin (IL)-10 and IL-6 proteins with enzyme-linked immunosorbent assay (ELISA). Results: Co-culture of PBMCs with ESCs or dESCs did not affect baseline proliferation, whereas co-culture with MSCs significantly suppressed baseline proliferation. Stimulation of PBMC proliferation by using super-antigens (sAgs) was also suppressed by co-culture with MSCs. Inhibition was greatest with direct contact, but significant inhibition was produced in transwell culture and by using MSC-conditioned media, suggesting that soluble factors play a role in MSC-mediated immune suppression. The MSCs constitutively secrete IL-6, even in the absence of co-culture with PBMCs. MSC-conditioned media also brought about a change in the cytokine-expression profile of sAg-stimulated PBMCs, significantly reducing PBMC expression of IL-6, IFN-γ, and TNF-α. Conclusions: Equine MSCs and ESCs possess a degree of innate immune privilege, and MSCs secrete soluble factors that suppress PBMC proliferation and alter cytokine expression. These properties may make possible the future clinical use of allogeneic stem cells to help standardize and broaden the scope of treatment of tissue injuries.
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Publication Date: 2014-07-30 PubMed ID: 25080326PubMed Central: PMC4247727DOI: 10.1186/scrt479Google Scholar: Lookup
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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 article investigates the immune-privileged properties of equine mesenchymal stem cells and embryo-derived stem cells, and their potential application in regenerative medicine.

Understanding the Research

The research paper focuses on the study of certain types of stem cells derived from horses, more specifically, mesenchymal stem cells (MSCs) and embryo-derived stem cells (ESCs).

  • The study begins by noting that these types of autologous cells (cells derived from the same individual undergoing therapy) are potentially beneficial for regenerative medicine but their functioning is not completely understood.
  • Historically, these cells have been seen to not elicit an immune response when injected into the tendon of a horse. Hence, the researchers assume that these cells have properties that make them immune-privileged.
  • The researchers aim to understand if these properties could be beneficial for therapeutic purposes in other tissues as well.

Methodology

Various experiments were conducted using these cells to understand their properties.

  • The MSCs, ESCs, and differentiated ESCs (dESCs) were treated with Mitomycin C and cultured with equine peripheral blood mononuclear cells (PBMCs).
  • The effect of these cells on PBMC proliferation (growth and multiplication) was observed both in the presence and absence of a certain protein called interferon-gamma (IFN-γ).
  • Additionally, co-culture of MSCs and PBMCs was performed directly or indirectly in transwells, and then the proliferation of PBMCs was examined.
  • Apart from these, the media or the solution in which these cells were grown was also studied for various cytokines—a type of protein that could play a key role in cell signaling.

Results

From these experiments, several key findings were observed.

  • The co-culture of PBMCs with ESCs or dESCs did not influence the baseline proliferation, whereas, in the presence of MSCs, baseline proliferation was significantly reduced.
  • The proliferation of PBMCs in the presence of super-antigens was also observed to be suppressed when co-cultured with MSCs. This suppression was seen to be greater when there was direct contact. However, considerable suppression was also observed in transwell culture and using MSC-conditioned media, indicating that soluble factors may have played a role in the immune-suppression carried out by MSCs.
  • It was also noted that the MSCs constantly secrete interleukin-6 (IL-6), regardless of whether they are being co-cultured with PBMCs or not.
  • Moreover, the media conditioned with MSCs led to a significant reduction in the expression of IL-6, IFN-γ, and TNF-α in the PBMCs stimulated by super-antigens.

Conclusions

In conclusion, the researchers noted that MSCs and ESCs in horses display a certain level of innate immune privilege. They also found that MSCs secrete certain soluble factors that can suppress PBMC proliferation and change cytokine expression. The authors suggest that these properties may lead to the future clinical use of allogeneic (donor-derived) stem cells, thereby expanding the scope and standardization of treatments for tissue injuries.

Cite This Article

APA
Paterson YZ, Rash N, Garvican ER, Paillot R, Guest DJ. (2014). Equine mesenchymal stromal cells and embryo-derived stem cells are immune privileged in vitro. Stem Cell Res Ther, 5(4), 90. https://doi.org/10.1186/scrt479

Publication

Stem cell research & therapy
ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 5
Issue: 4
Pages: 90
PII: 90

Researcher Affiliations

Paterson, Yasmin Z
    Rash, Nicola
      Garvican, Elaine R
        Paillot, Romain
          Guest, Deborah J

            MeSH Terms

            • Animals
            • Horse Diseases / therapy
            • Mesoderm / cytology
            • Stem Cell Transplantation / veterinary
            • Stem Cells / cytology
            • Tendon Injuries / veterinary
            • Tendons / cytology

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