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Equine veterinary journal2020; 52(4); 601-612; doi: 10.1111/evj.13222

Single and repeated intra-articular injections in the tarsocrural joint with allogeneic and autologous equine bone marrow-derived mesenchymal stem cells are safe, but did not reduce acute inflammation in an experimental interleukin-1β model of synovitis.

Abstract: Allogeneic and autologous bone marrow-derived mesenchymal stem cells (BMDMSCs) have been administered in equine joints for their anti-inflammatory effects. However, allogeneic BMDMSC offer multiple clinical and practical advantages. Therefore, it is important to determine the relative effectiveness of allogeneic vs autologous BMDMSCs. Objective: The objective of the study was to compare the inflamed joint response to autologous vs allogeneic BMDMSCs injections, and to determine if either treatment generated an anti-inflammatory effect. Methods: Randomised controlled study. Methods: Bone marrow was harvested from eight horses. Autologous BMDMSCs and pooled allogeneic BMDMSCs were culture expanded, cryopreserved and thawed immediately prior to administration. Ten million autologous BMDMSCs were administered with 75 ng rIL-1β into one tarsocrural joint and the contralateral tarsocrural joint received allogeneic BMDMSC plus 75 ng rIL-1β. Repeat injections were performed with the same treatment administered into the same joint. Four additional horses received 75 ng rIL-1β alone in a single tarsocrural joint. Clinical parameters (lameness, joint circumference and joint effusion) and synovial fluid parameters, including nucleated cell count (NCC), differential cell count, total protein (TP), prostaglandin E2 (PGE2 ) and C-reactive protein (CRP), were measured at baseline, 6, 12, 24, 72, 168 and 336 hours post-injection. Results: No difference was detected between autologous and allogeneic treatment groups with respect to subjective lameness, joint effusion, joint circumference, NCC, TP, differential cell count, CRP or PGE2 . Neither autologous nor allogeneic treatments resulted in an improvement in clinical or cytological parameters over that elicited by rIL-1β alone. Conclusions: A single dose of rIL-1β was evaluated and resulted in a severe synovitis which may have been too severe to observe a BMDMSC-mediated effect. Conclusions: This study revealed that allogeneic and autologous BMDMSCs resulted in an equivalent clinical and cytological response. Allogeneic and autologous BMDMSCs were equally ineffective in reducing the inflammatory response from acute rIL-1β-induced joint inflammation in horses.
© 2019 EVJ Ltd.
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Publication Date: 2020-02-14 PubMed ID: 31821594PubMed Central: PMC7283005DOI: 10.1111/evj.13222Google 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 study investigated the impact of autologous and allogeneic bone marrow-derived mesenchymal stem cells (BMDMSCs) on inflammation within the joints of horses, finding that neither type of BMDMSC offered an anti-inflammatory effect in an experimental model of severe synovitis.

Objective and Methodology

The researchers aimed to compare the response of inflamed equine joints to both autologous (stem cells from the same individual) and allogeneic (stem cells from a different individual) BMDMSCs, with the goal of determining if either form of treatment yielded an anti-inflammatory effect.

  • Bone marrow was collected from eight horses, with both autologous and pooled allogeneic BMDMSCs being cultivated, frozen, and then thawed immediately before being used.
  • Each horse had one joint treated with autologous BMDMSCs combined with 75 ng rIL-1β (a pro-inflammatory cytokine); the other joint was treated with allogeneic BMDMSCs and the same dose of rIL-1β.
  • The process was then replicated, with the same treatments being given to the same joints. Four additional horses were given 75 ng rIL-1β alone to serve as controls.

Parameters and Measurements

Numerous clinical and synovial fluid parameters were monitored and measured at a series of time points after injection, including:

  • Level of lameness
  • Joint size and joint fluid quantity
  • Synovial fluid elements, such as nucleated cell count (NCC), differential cell count, total protein (TP), prostaglandin E (PGE) and C-reactive proteins (CRP)

Results of the Study

The results suggested that there was no significant difference between the autologous and allogeneic treatment groups in terms of lameness, joint swelling, synovial fluid measures or cytological parameters. Notably, neither the autologous nor allogeneic treatments resulted in an improvement greater than that evoked by rIL-1β on its own.

Conclusions

The research found that a single dose of rIL-1β led to severe synovitis, a condition possibly too intense for any potential BMDMSC-mediated impact to be discernible. The findings showed that both types of BMDMSC treatment had equivalent clinical and cytological outcomes, which unfortunately were ineffective in reducing the inflammation caused by acute rIL-1β-triggered joint inflammation in the horses. As such, further research is needed to determine the potential therapeutic value of BMDMSCs in managing joint inflammation.

Cite This Article

APA
Colbath AC, Dow SW, Hopkins LS, Phillips JN, McIlwraith CW, Goodrich LR. (2020). Single and repeated intra-articular injections in the tarsocrural joint with allogeneic and autologous equine bone marrow-derived mesenchymal stem cells are safe, but did not reduce acute inflammation in an experimental interleukin-1β model of synovitis. Equine Vet J, 52(4), 601-612. https://doi.org/10.1111/evj.13222

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 52
Issue: 4
Pages: 601-612

Researcher Affiliations

Colbath, Aimée C
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Dow, Steven W
  • Center for Immune and Regenerative Medicine, Department of Clinical Sciences, College of Veterinary Medicine, Colorado State University, Fort Collins, Colorado, USA.
Hopkins, Leone S
  • Department of Clinical Sciences, College of Veterinary Medicine, College of Veterinary Medicine, Colorado State University, Fort Collins, Colorado, USA.
Phillips, Jennifer N
  • Orthopedic Research Center, C. Wayne McIlwraith Translational Medicine Institute, Department of Clinical Sciences, College of Veterinary Medicine, Colorado State University, Fort Collins, Colorado, USA.
McIlwraith, C Wayne
  • Orthopedic Research Center, C. Wayne McIlwraith Translational Medicine Institute, Department of Clinical Sciences, College of Veterinary Medicine, Colorado State University, Fort Collins, Colorado, USA.
Goodrich, Laurie R
  • Orthopedic Research Center, C. Wayne McIlwraith Translational Medicine Institute, Department of Clinical Sciences, College of Veterinary Medicine, Colorado State University, Fort Collins, Colorado, USA.

MeSH Terms

  • Animals
  • Bone Marrow
  • Hematopoietic Stem Cell Transplantation / veterinary
  • Horse Diseases
  • Horses
  • Inflammation / veterinary
  • Injections, Intra-Articular / veterinary
  • Interleukin-1beta
  • Mesenchymal Stem Cell Transplantation / veterinary
  • Mesenchymal Stem Cells
  • Synovial Fluid
  • Synovitis / veterinary

Grant Funding

  • T32 OD010437 / NIH HHS
  • NIH, National Research Service Award
  • Grayson-Jockey Club Research Foundation
  • Wayne and Nancy McIlwraith Fellowship

Conflict of Interest Statement

Authors’ declaration of interests. No competing interests have been declared.

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Citations

This article has been cited 9 times.
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