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Home / Equine Research Bank / Stem Cell Res Ther / Multiple intravenous injections of allogeneic equine mesench...
Stem cell research & therapy2015; 6(1); 73; doi: 10.1186/s13287-015-0050-0

Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses.

Abstract: Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses. Methods: We injected three doses of 25 × 10(6) allogeneic MSCs from either AT or BM (a total of 75 × 10(6) MSCs per horse) into five and five, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response, including total leukocyte numbers, serum cytokine concentration, and splenic lymphocyte subsets. Results: Repeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any clinical adverse effects. Repeated BM-MSC injection resulted in increased blood CD8(+) T-cell numbers. Multiple BM-MSC injections also increased splenic regulatory T cell numbers compared with AT-MSC-injected horses but not controls. Conclusions: These data demonstrate that multiple IV injections of allogeneic MSCs are well tolerated by healthy horses. No clinical signs or clinico-pathologic measurements of organ toxicity or systemic inflammatory response were recorded. Increased numbers of circulating CD8(+) T cells after multiple IV injections of allogeneic BM-MSCs may indicate a mild allo-antigen-directed cytotoxic response. Safety and efficacy of allogeneic MSC IV infusions in sick horses remain to be determined.
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Publication Date: 2015-04-15 PubMed ID: 25888916PubMed Central: PMC4446064DOI: 10.1186/s13287-015-0050-0Google 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.

This study examines the safety and effects of multiple intravenous injections of allogeneic mesenchymal stem cells (MSCs) in healthy horses. The study found that multiple injections do not trigger a systemic inflammatory response or any apparent adverse clinical effects, but do cause changes in lymphocyte subsets.

Research Purpose and Methodology

  • The aim of this research was to determine the safety and immune response of multiple intravenous injections of allogeneic stem cells in horses, specifically cells derived from adipose tissue (AT-MSCs) or bone marrow (BM-MSCs).
  • A total of ten healthy horses were studied. Each received three doses of 25 × 10(6) allogeneic MSCs from either adipose tissue or bone marrow, a total of 75 × 10(6) MSCs per horse.
  • The horses were monitored for 35 days following the initial infusion of MSCs. The researchers evaluated clinical signs, organ function, inflammatory and immune response including overall leukocyte numbers, serum cytokine levels, and splenic lymphocyte subsets.

Findings

  • The study found that repeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any apparent clinical adverse effects indicating that the procedure was well-tolerated.
  • There were no signs of organ toxicity or systemic inflammatory response recorded in any of the horses studied, suggesting the procedure did not trigger a significant immune reaction that could lead to a broad inflammatory response.
  • Nonetheless, repeated injections of BM-MSCs did lead to an increase in blood CD8(+) T-cell counts, a type of lymphocyte that can have a role in immune response. Multiple BM-MSC injections also resulted in increased numbers of splenic regulatory T cells compared with AT-MSC-injected horses, although no increase was observed compared to controls not receiving MSCs.

Conclusions

  • The data from this research demonstrate that multiple allogeneic MSC infusions can be safely administered to horses, with no adverse clinical effects or significant immune response detected.
  • However, the increase in CD8(+) T cells following repeated BM-MSC injections suggests a mild cytotoxic response to allo-antigens may occur. This response was not seen in horses receiving AT-MSCs.
  • The study concludes by noting that the safety and efficacy of allogeneic MSC infusions in ill horses remain to be determined as this study only evaluated healthy horses.

Cite This Article

APA
Kol A, Wood JA, Carrade Holt DD, Gillette JA, Bohannon-Worsley LK, Puchalski SM, Walker NJ, Clark KC, Watson JL, Borjesson DL. (2015). Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses. Stem Cell Res Ther, 6(1), 73. https://doi.org/10.1186/s13287-015-0050-0

Publication

Stem cell research & therapy
ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 6
Issue: 1
Pages: 73
PII: 73

Researcher Affiliations

Kol, Amir
  • Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA, 95616, USA. akol@ucdavis.edu.
Wood, Joshua A
  • Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA, 95616, USA. jawood@ucdavis.edu.
Carrade Holt, Danielle D
  • Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA, 95616, USA. ddcarrade@ucdavis.edu.
Gillette, Jessica A
  • Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA, 95616, USA. jagillette@ucdavis.edu.
Bohannon-Worsley, Laurie K
  • Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA, 95616, USA. lkbohannon@ucdavis.edu.
Puchalski, Sarah M
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA. smpuchalski@ucdavis.edu.
Walker, Naomi J
  • Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA, 95616, USA. njwalker@ucdavis.edu.
Clark, Kaitlin C
  • Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA, 95616, USA. kcclark@ucdavis.edu.
Watson, Johanna L
  • Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA. jlwatson@ucdavis.edu.
Borjesson, Dori L
  • Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA, 95616, USA. dlborjesson@ucdavis.edu.

MeSH Terms

  • Adipose Tissue / cytology
  • Animals
  • Bone Marrow Cells / cytology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Cytokines / blood
  • Enzyme-Linked Immunosorbent Assay
  • Forkhead Transcription Factors / metabolism
  • Horses
  • Injections, Intravenous
  • Lymphocyte Subsets / cytology
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Systemic Inflammatory Response Syndrome
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Transplantation, Homologous

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