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Cytotherapy2011; 13(10); 1180-1192; doi: 10.3109/14653249.2011.602338

Intradermal injections of equine allogeneic umbilical cord-derived mesenchymal stem cells are well tolerated and do not elicit immediate or delayed hypersensitivity reactions.

Abstract: BACKGROUND AIMS. The use of allogeneic mesenchymal stem cells (MSC) to treat acute equine lesions would greatly expand equine cellular therapy options; however, the safety and antigenicity of these cells have not been well-studied. We hypothesized that equine allogeneic umbilical cord tissue (UCT)-derived MSC would not elicit acute graft rejection or a delayed-type hypersensitivity response when injected intradermally. METHODS. Six Quarterhorse yearlings received 12 intradermal injections (autologous MSC, allogeneic MSC, positive control and negative control, in triplicate) followed by the same series of 12 injections, 3-4 weeks later, at another site. Wheals were measured and palpated at 0.25, 4, 24, 48, 72 h and 7 days post-injection. Biopsies were obtained at 48 and 72 h and 7 days post-injection. Mixed leukocyte reactions were performed 1 week prior to the first injections and 3 weeks after the second injections. RESULTS. There were no adverse local or systemic responses to two intradermal injections of allogeneic MSC. MSC injection resulted in minor wheal formation, characterized by mild dermatitis, dermal edema and endothelial hyperplasia, that fully resolved by 48-72 h. No differences were noted between allogeneic and autologous MSC. The second injection of MSC did not elicit more significant physical or histomorphologic alterations compared with the first MSC injection. Neither allogeneic nor autologous UCT-derived MSC stimulated or suppressed baseline T-cell proliferation in vitro prior to or after two MSC administrations. CONCLUSIONS. Equine allogeneic UCT MSC may be safely administered intradermally on multiple occasions without eliciting a measurable cellular immune response.
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Publication Date: 2011-09-07 PubMed ID: 21899391DOI: 10.3109/14653249.2011.602338Google 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 investigates the safety and antigenicity of mesenchymal stem cells derived from equine umbilical cord tissue when injected into horses. The results suggest that these stem cells do not cause immediate or delayed hypersensitivity reactions and can be administered safely.

Research Background and Aims

  • The researchers are studying the potential of using mesenchymal stem cells (MSC) from umbilical cord tissue (UCT) of horses to treat acute lesions in the same species.
  • Such use of allogeneic stem cells (from a different individual of the same species) would present new avenues in equine cellular therapy but their safety and antigenicity (ability to provoke an immune response) needs to be thoroughly tested.

Research Methodology

  • Six Quarterhorse yearlings (one-year-old horses) were given 12 intradermal (into the skin) injections. These injections comprised different variations: autologous MSCs (stem cells from the same individual), allogeneic MSCs, positive control, and negative control, each repeated three times.
  • This series of injections was repeated after 3-4 weeks at another site of the body.
  • Observations were made at several points in time after the injections, with biopsy samples taken at the 48-hour, 72-hour, and 7-day marks post-injection to study the physical and histological changes. In addition, mixed leukocyte reactions were performed a week before the first injections and three weeks after the second injections to study the immune response.

Findings of the Research

  • The results indicated that the horses did not show any adverse local or systemic responses to the injections of allogeneic MSCs.
  • The MSC injection led to a small amount of swelling accompanied by mild dermatitis, skin edema, and endothelial hyperplasia. These symptoms resolved within 48-72 hours. No differences were observed between the reactions to autologous and allogeneic MSCs.
  • A second injection of MSCs did not trigger any significant changes in comparison to the first one.
  • The researchers also found no evidence of T-cell proliferation (a sign of an immune response) in the lab, either before or after the administration of MSCs, suggesting that these cells do not elicit a measurable cellular immune response.

Conclusions of the Study

  • The study concludes that MSCs derived from equine allogenic UCT can be safely applied intradermally on multiple occasions in horses, without provoking a cellular immune response. This makes them a promising option for treating acute lesions in horses.

Cite This Article

APA
Carrade DD, Affolter VK, Outerbridge CA, Watson JL, Galuppo LD, Buerchler S, Kumar V, Walker NJ, Borjesson DL. (2011). Intradermal injections of equine allogeneic umbilical cord-derived mesenchymal stem cells are well tolerated and do not elicit immediate or delayed hypersensitivity reactions. Cytotherapy, 13(10), 1180-1192. https://doi.org/10.3109/14653249.2011.602338

Publication

Cytotherapy
ISSN: 1477-2566
NlmUniqueID: 100895309
Country: England
Language: English
Volume: 13
Issue: 10
Pages: 1180-1192

Researcher Affiliations

Carrade, Danielle D
  • Departments of Pathology, Microbiology and Immunology, School of Veterinary, University of California, USA.
Affolter, Verena K
    Outerbridge, Catherine A
      Watson, Johanna L
        Galuppo, Larry D
          Buerchler, Sabine
            Kumar, Vijay
              Walker, Naomi J
                Borjesson, Dori L

                  MeSH Terms

                  • Animals
                  • Cell Proliferation
                  • Horses
                  • Hypersensitivity, Delayed / etiology
                  • Hypersensitivity, Delayed / prevention & control
                  • Hypersensitivity, Immediate / etiology
                  • Hypersensitivity, Immediate / prevention & control
                  • Lymphocyte Activation / immunology
                  • Lymphocyte Culture Test, Mixed
                  • Mesenchymal Stem Cell Transplantation
                  • Mesenchymal Stem Cells / cytology
                  • Mesenchymal Stem Cells / immunology
                  • Mesenchymal Stem Cells / metabolism
                  • Postoperative Complications
                  • T-Lymphocytes / immunology
                  • Umbilical Cord / cytology

                  Grant Funding

                  • R43AG033965 / NIA NIH HHS

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