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Equine veterinary journal2015; 48(2); 253-260; doi: 10.1111/evj.12414

Donor-derived equine mesenchymal stem cells suppress proliferation of mismatched lymphocytes.

Abstract: Recently, it has been shown that mesenchymal stem cells (MSCs) do not express the major histocompatibility complex (MHC) II antigen and are able to inhibit proliferation of MHC-mismatched stimulated lymphocytes, enabling their use as in vivo allogeneic transplants. However, prior to clinical application of allo-MSCs, in vitro tests are required to confirm the safety of treatment protocols. Objective: To evaluate the immunosuppressive capabilities of equine bone-marrow-derived MSCs (BM-MSCs) on MHC-mismatched lymphocytes. Methods: In vitro experiment. Methods: Phytohaemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs) from 3 Thoroughbreds (recipients) were co-cultured with mismatched BM-MSCs from 3 Connemara ponies (donors). Proliferation of lymphocytes was monitored by carboxyfluorescein succinimidyl ester labelling and analysed by flow cytometry. In total, 6 horses were haplotyped using microsatellites to confirm mismatching. Optimisation of the conditions to stimulate Thoroughbred lymphocytes and titration of equine anti-CD4 and anti-CD8 antibodies were performed. Connemara pony and Thoroughbred BM-MSCs were isolated, expanded and characterised by tri-lineage differentiation. Finally, BM-MSCs from both breeds were set up in co-culture at different ratios with stimulated Thoroughbred lymphocytes. Proliferation of CD4(+) and CD8(+) cells was determined by flow cytometry. Results: A high proportion of CD4/CD8 double-positive lymphocytes were found in freshly isolated PBMCs, although this percentage decreased after 4 days of culture. Mismatched BM-MSCs inhibited proliferation of stimulated lymphocytes in a dose-dependent manner, with the greatest suppression occurring at a 1:10 ratio of BM-MSCs to PBMCs. Proliferation of CD4(+) and CD8(+) subpopulations decreased in 1:10 co-culture, with statistical significance in the case of CD8(+) cells, while that of the CD4/CD8 double-positive population was similar to the phytohaemagglutinin control. Conclusions: The results demonstrate dose-dependent immunosuppression of stimulated lymphocytes by mismatched equine BM-MSCs, supporting their future application in allo-MSC clinical treatments.
© 2015 EVJ Ltd.
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Publication Date: 2015-03-05 PubMed ID: 25582202DOI: 10.1111/evj.12414Google 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 study investigates the ability of equine bone marrow-derived mesenchymal stem cells (BM-MSCs) to suppress the activity of mismatched lymphocytes, a type of immune cell. The study finds that these stem cells can indeed inhibit such activity, suggesting potential for future clinical use in stem-cell treatment.

Research Purpose and Methods

  • The research aims to assess the immune-suppressing capabilities of equine (horse) BM-MSCs on mismatched lymphocytes.
  • Mesenchymal stem cells (MSCs) do not express the major histocompatibility complex (MHC) II antigen, which is a protein vital in the immune response. This characteristic makes these cells a promising option for transplant therapies.
  • The study involved an in-vitro experiment, where peripheral blood mononuclear cells (PBMCs) from three Thoroughbreds were co-cultured with mismatched BM-MSCs from three Connemara ponies.
  • Lymphocyte proliferation (growth and multiplication) was monitored using a technique known as carboxyfluorescein succinimidyl ester (CFSE) labeling and then analyzed using a method known as flow cytometry.
  • The study also involved checking the equine breeds for their MHC markers and testing the optimum conditions to stimulate lymphocytes.

Study Findings

  • The study observed that a high proportion of lymphocytes that expressed both CD4 and CD8 markers were found in freshly isolated PBMCs. However, this percentage decreased over four days of culture.
  • Bone marrow-derived MSCs from donor ponies suppressed the proliferation of stimulated lymphocytes in a dose-dependent manner. The highest level of suppression occurred when the ratio of BM-MSCs to PBMCs was 1:10.
  • Proliferation of both CD4 and CD8 cells decreased in the 1:10 co-culture, with statistical significance in the case of CD8 cells. However, the proliferation of cells expressing both CD4 and CD8 markers was similar to the control group.

Conclusions and Implications

  • The results indicated that mismatched equine BM-MSCs have a dose-dependent immunosuppressive effect on stimulated lymphocytes.
  • This finding supports the potential future use of allo-MSC clinical treatments, which use cells from a donor of the same species but with a different genetic profile.
  • Such treatments could possibly be helpful in controlling undesirable immune responses in various clinical applications, especially in transplants.

Cite This Article

APA
Ranera B, Antczak D, Miller D, Doroshenkova T, Ryan A, McIlwraith CW, Barry F. (2015). Donor-derived equine mesenchymal stem cells suppress proliferation of mismatched lymphocytes. Equine Vet J, 48(2), 253-260. https://doi.org/10.1111/evj.12414

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 48
Issue: 2
Pages: 253-260

Researcher Affiliations

Ranera, B
  • Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, Galway, Ireland.
Antczak, D
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Miller, D
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Doroshenkova, T
  • Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, Galway, Ireland.
Ryan, A
  • Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, Galway, Ireland.
McIlwraith, C W
  • Orthopaedic Research Center, Colorado State University, Fort Collins, USA.
Barry, F
  • Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, Galway, Ireland.

MeSH Terms

  • Animals
  • Bone Marrow Cells
  • Cell Proliferation / physiology
  • Coculture Techniques
  • Histocompatibility Testing
  • Horses
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / physiology
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / physiology
  • Major Histocompatibility Complex / genetics
  • Major Histocompatibility Complex / immunology
  • Mesenchymal Stem Cells / physiology
  • Phytohemagglutinins / toxicity

Citations

This article has been cited 14 times.
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