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Journal of veterinary internal medicine2022; 36(4); 1491-1501; doi: 10.1111/jvim.16447

Effects of intravenous administration of peripheral blood-derived mesenchymal stromal cells after infusion of lipopolysaccharide in horses.

Abstract: A systemic and dysregulated immune response to infection contributes to morbidity and mortality associated with sepsis. Peripheral blood-derived mesenchymal stromal cells (PB-MSC) mitigate inflammation in animal models of sepsis. Allogeneic PB-MSC administered IV to horses is well-tolerated but therapeutic benefits are unknown. Objective: After IV lipopolysaccharide (LPS) infusion, horses treated with PB-MSC would have less severe clinical signs, clinicopathological abnormalities, inflammatory cytokine gene expression, and oxidative stress compared to controls administered a placebo. Methods: Sixteen horses were included in this study. Methods: A randomized placebo-controlled experimental trial was performed. Sixteen healthy horses were assigned to 1 of 2 treatment groups (1 × 10  PB-MSC or saline placebo). Treatments were administered 30 minutes after completion of LPS infusion of approximately 30 ng/kg. Clinical signs, clinicopathological variables, inflammatory cytokine gene expression, and oxidative stress markers were assessed at various time points over a 24-hour period. Results: A predictable response to IV LPS infusion was observed in all horses. At the dose administered, there was no significant effect of PB-MSC on clinical signs, clinicopathological variables, or inflammatory cytokine gene expression at any time point. Antioxidant potential was not different between treatment groups, but intracellular ROS increased over time in the placebo group. Other variables that changed over time were likely due to effects of IV LPS infusion. Conclusions: Administration of allogeneic PB-MSC did not cause clinically detectable adverse effects in healthy horses. The dose of PB-MSC used here is unlikely to exert a beneficial effect in endotoxemic horses.
© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
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Publication Date: 2022-06-14 PubMed ID: 35698909PubMed Central: PMC9308407DOI: 10.1111/jvim.16447Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

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 is a scientific study investigating the impact of administering mesenchymal stromal cells derived from peripheral blood (PB-MSC) to horses after inducing a systemic inflammatory response. It concludes that while the PB-MSC do not cause adverse effects, they also did not present noticeable benefits in treating the induced inflammatory condition at the administered dose.

Objective of the Study

The main goal of this study was to investigate whether treating horses with PB-MSC after inducing a systemic inflammatory response with lipopolysaccharide (LPS), would reduce clinical signs of inflammation, pathological abnormalities, inflammatory cytokine gene expression and oxidative stress compared to horses treated with a placebo.

Methodology

  • Sixteen healthy horses were randomly assigned into two treatment groups— each receiving either an intravenous dose of PB-MSC or a saline placebo.
  • The treatments were administered half an hour post completion of the LPS infusion, which was given at approximately 30 nanogrammes per kilogramme of the horse’s body weight.
  • Various parameters such as clinical signs, pathological variables, inflammatory cytokine gene expression, and markers of oxidative stress were assessed at different time points over a twenty-four-hour period.

Results

  • All the horses reacted in a predictable manner to the intravenous infusion of LPS.
  • The administration of PB-MSC did not have any significant effect on the clinical symptoms, pathological changes, or gene expressions related to inflammation at any point in time.
  • The antioxidant potential remained unchanged across both treatment groups, but there was an observed increase in intracellular Reactive Oxygen Species (ROS) with time in the group that received the placebo.
  • Other variables that changed over time were attributed to the effects of the intravenous infusion of LPS.

Conclusion

The authors concluded that the administration of allogeneic PB-MSC caused no clinically detectable adverse effects in the horses. However, they also stated that the dose of PB-MSC used in this study is unlikely to exert a beneficial effect in treating horses with endotoxemic conditions. This suggests that while PB-MSC may be safely administered to horses, the therapeutic benefits at the administered dose were inconclusive, justifying further examination at different dosages or administration methods.

Cite This Article

APA
Taylor SD, Serpa PBS, Santos AP, Hart KA, Vaughn SA, Moore GE, Mukhopadhyay A, Page AE. (2022). Effects of intravenous administration of peripheral blood-derived mesenchymal stromal cells after infusion of lipopolysaccharide in horses. J Vet Intern Med, 36(4), 1491-1501. https://doi.org/10.1111/jvim.16447

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 36
Issue: 4
Pages: 1491-1501

Researcher Affiliations

Taylor, Sandra D
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.
Serpa, Priscila B S
  • Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.
Santos, Andrea P
  • Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.
Hart, Kelsey A
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
Vaughn, Sarah A
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
Moore, George E
  • Department of Veterinary Administration, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.
Mukhopadhyay, Abhijit
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.
Page, Allen E
  • Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.

MeSH Terms

  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • Endotoxemia / veterinary
  • Horse Diseases / drug therapy
  • Horses
  • Infusions, Intravenous / veterinary
  • Lipopolysaccharides
  • Mesenchymal Stem Cells / metabolism

Grant Funding

  • 1016369 / USDA National Institute of Food and Agriculture
  • Purdue University AgSEED Agricultural Research and Extension Program
  • 208453 / Purdue University Showalter Trust

Conflict of Interest Statement

George E. Moore serves as Consulting Editor for Experimental Design and Statistics for the Journal of Veterinary Internal Medicine. He was not involved in review of this manuscript. No other authors have a conflict of interest.

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Citations

This article has been cited 3 times.
  1. Mukhopadhyay A, Cook SR, SanMiguel P, Ekenstedt KJ, Taylor SD. TLR4 and MD2 variation among horses with differential TNFα baseline concentrations and response to intravenous lipopolysaccharide infusion. Sci Rep 2023 Jan 27;13(1):1486.
    doi: 10.1038/s41598-023-27956-ypubmed: 36707633google scholar: lookup
  2. Cassano JM, Leonard BC, Martins BC, Vapniarsky N, Morgan JT, Dow SW, Wotman KL, Pezzanite LM. Preliminary evaluation of safety and migration of immune activated mesenchymal stromal cells administered by subconjunctival injection for equine recurrent uveitis. Front Vet Sci 2023;10:1293199.
    doi: 10.3389/fvets.2023.1293199pubmed: 38162475google scholar: lookup
  3. Taylor SD, Hart KA, Vaughn S, Giancola SC, Serpa PBS, Santos AP. Effects of intravenous administration of ascorbic acid (vitamin C) on oxidative status in healthy adult horses. J Vet Intern Med 2024 Jan-Feb;38(1):460-468.
    doi: 10.1111/jvim.16934pubmed: 37948618google scholar: lookup
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