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Veterinary immunology and immunopathology2020; 231; 110146; doi: 10.1016/j.vetimm.2020.110146

Do allogeneic bone marrow derived mesenchymal stem cells diminish the inflammatory response to lipopolysaccharide infusion in horses? A pilot study.

Abstract: Endotoxemia is a leading cause of morbidity and mortality in the equine industry, with colic being the most common cause of endotoxemia in horses. The objective of this study was to evaluate the safety and potential efficacy of a single dose of allogeneic equine bone marrow derived mesenchymal stem cells (BM-MSCs) in horses after the IV administration of lipopolysaccharide (LPS). Six horses were administered an IV infusion of 30 ng/kg LPS (O55:B5 Escherichia coli) in 500 ml saline over 30 min. Immediately after infusion test horses (n = 3) were administered 100 × 10 allogeneic BM-MSCs diluted in saline IV and control horses (n = 3) were administered saline. Clinicopathological data, pro-inflammatory cytokine measurements and sCD14 concentrations were compared between groups. No adverse reactions were observed in horses administered BM-MSCs intravenously. There were no significant differences between test and control horses with regard to clinicopathological values or pro-inflammatory cytokine production. At no time point did concentrations of sCD14 exceed the reference range in any horse. Results suggest that administration of a single IV dose of freshly cultured MSCs is safe and well-tolerated in horses with induced endotoxemia. Further study to evaluate their efficacy as a potential therapeutic in a larger number of horses with clinical disease is required.
Publication Date: 2020-11-02 PubMed ID: 33221572DOI: 10.1016/j.vetimm.2020.110146Google Scholar: Lookup
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  • Clinical Trial
  • Veterinary
  • Journal Article

Summary

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This research aimed to investigate the safety and possible effectiveness of providing a single IV dose of allogeneic equine bone marrow derived mesenchymal stem cells (BM-MSCs) to reduce the effects of endotoxemia in horses. The results show that a single treatment is safe and tolerable, but showed no significant effect on clinical pathology or pro-inflammatory cytokine production.

Research Objective

  • The main goal of this pilot study was to examine the potential for allogenic bone marrow derived mesenchymal stem cells (BM-MSCs) to reduce the inflammatory response in horses suffering from endotoxemia, a serious condition related to instances of colic, a common ailment in horses.

Study Methodology

  • In order to test their hypothesis, the researchers induced endotoxemia in six horses via the IV administration of lipopolysaccharide (LPS).
  • Subsequently, three of these horses (the test subjects) were given an IV infusion of 100 × 10 allogeneic BM-MSCs, suspended in saline. The remaining three horses (the control group) received only the saline.
  • Over the course of the experiment, the researchers monitored for adverse reactions and examined clinicopathological data and pro-inflammatory cytokine production. Furthermore, they also examined soluble CD14 (sCD14), a co-receptor that is involved in the immune response to bacterial lipopolysaccharide.

Key Findings

  • No immediate adverse reactions were reported in the horses that were treated with the BM-MSCs via intravenous administration.
  • There were no significant differences observed in clinicopathological values or the production of pro-inflammatory cytokines between the test and control groups.
  • sCD14 concentrations did not exceed the reference range in any horse.

Conclusions and Implications

  • The researchers concluded that a single administration of freshly-cultured MSCs is safe and well-tolerated in horses with induced endotoxemia.
  • However, they also concluded that there were no significant changes seen in clinicopathological markers or pro-inflammatory cytokine production, suggesting that this treatment might not have an immediate obvious effect on reducing the symptoms of endotoxemia.
  • Therefore, the researchers advise that further study involving a larger sample size and possibly longer-term observation needs to be conducted in order to develop a better understanding of the therapeutic potential of this treatment for endotoxemia in horses.

Cite This Article

APA
Kilcoyne I, Nieto JE, Watson JL, Galuppo LD, Borjesson DL. (2020). Do allogeneic bone marrow derived mesenchymal stem cells diminish the inflammatory response to lipopolysaccharide infusion in horses? A pilot study. Vet Immunol Immunopathol, 231, 110146. https://doi.org/10.1016/j.vetimm.2020.110146

Publication

ISSN: 1873-2534
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 231
Pages: 110146
PII: S0165-2427(20)30172-0

Researcher Affiliations

Kilcoyne, Isabelle
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California at Davis, CA, United States. Electronic address: ikilcoyne@ucdavis.edu.
Nieto, Jorge E
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California at Davis, CA, United States.
Watson, Johanna L
  • Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California at Davis, CA, United States.
Galuppo, Larry D
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California at Davis, CA, United States.
Borjesson, Dori L
  • Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California at Davis, CA, United States.

MeSH Terms

  • Animals
  • Female
  • Horses / immunology
  • Infusions, Intravenous / veterinary
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / immunology
  • Male
  • Mesenchymal Stem Cell Transplantation / veterinary
  • Mesenchymal Stem Cells / immunology

Citations

This article has been cited 2 times.
  1. Taylor SD, Serpa PBS, Santos AP, Hart KA, Vaughn SA, Moore GE, Mukhopadhyay A, Page AE. Effects of intravenous administration of peripheral blood-derived mesenchymal stromal cells after infusion of lipopolysaccharide in horses.. J Vet Intern Med 2022 Jul;36(4):1491-1501.
    doi: 10.1111/jvim.16447pubmed: 35698909google scholar: lookup
  2. Cequier A, Sanz C, Rodellar C, Barrachina L. The Usefulness of Mesenchymal Stem Cells beyond the Musculoskeletal System in Horses.. Animals (Basel) 2021 Mar 25;11(4).
    doi: 10.3390/ani11040931pubmed: 33805967google scholar: lookup