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Equine veterinary journal2019; 52(1); 144-151; doi: 10.1111/evj.13136

Allogeneic vs. autologous intra-articular mesenchymal stem cell injection within normal horses: Clinical and cytological comparisons suggest safety.

Abstract: Allogeneic bone marrow-derived mesenchymal stem cells (BMDMSCs) could provide multiple advantages over autologous BMDMSCs, including creating an 'off-the-shelf' treatment together with the ability to control for donor variation. Objective: The objective of the study was to compare the clinical and synovial fluid response of the normal equine joint to autologous and pooled-allogeneic BMDMSCs while controlling for individual variation and joint variations in response to intra-articular injections. We hypothesised that, by controlling for individual animal and joint variation, we could identify differences between allogeneic vs. autologous BMDMSCs in noninflamed joints. Methods: Randomised-controlled experiment. Methods: Bone marrow was harvested from eight horses. Autologous BMDMSCs were culture expanded, cryopreserved and thawed immediately prior to administration. For allogeneic BMDMSC treatments, four horses' BMDMSCs were culture expanded, pooled, cryopreserved and thawed immediately prior to use. Ten million (autologous or pooled-allogeneic) BMDMSCs were administered into contralateral forelimb metacarpophalangeal joints so that every autologous and allogeneic injection could be compared within the same animal. Clinical parameters included subjective lameness, objective lameness (Lameness Locator™), response to flexion, joint circumference and joint effusion. Arthrocentesis was performed for assessment of the nucleated cell count, differential cell count, total protein, and synovial concentrations of prostaglandin E2 (PGE2) and c-reactive protein (CRP). All parameters were measured at baseline, 6, 12, 24, 72, 168 and 336 h post-injection. Results: No difference was detected in any parameters between forelimb metacarpophalangeal joints administered autologous or pooled-allogeneic BMDMSCs. Conclusions: This study did not attempt to measure efficacy of BMDMSCs for musculoskeletal disease and should be followed by properly controlled efficacy trials. Conclusions: The study did not identify any clinical or cytological differences in the normal joint response to allogeneic or autologous BMDMSCs. A larger study to prove equivalence is warranted as allogeneic BMDMSCs may be a feasible alternative to autologous BMDMSCs.
© 2019 EVJ Ltd.
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Publication Date: 2019-06-24 PubMed ID: 31120574DOI: 10.1111/evj.13136Google 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 aims to compare the effects of autologous and allogeneic bone marrow-derived mesenchymal stem cells (BMDMSCs) when injected into noninflamed joints of normal horses. The results show no significant clinical or cytological differences, suggesting allogeneic BMDMSCs may be a viable alternative to autologous BMDMSCs.

Objective and Hypothesis of the Study

  • The primary objective of this research was to compare the response of a normal horse’s joint to autologous (self-derived) and allogeneic (derived from a different individual) BMDMSCs.
  • The researchers controlled the conditions to account for individual and joint variations, with the hypothesis that this would enable them to spot any differences in the joint responses to the two types of cells in noninflamed joints.

Methodology

  • Bone marrow was harvested from eight horses.
  • For autologous treatment, BMDMSCs were cultured, preserved at low temperature (cryopreserved), and thawed right before administration.
  • For allogeneic treatments, BMDMSCs from four horses were cultured, combined, cryopreserved, and thawed just before use.
  • The injections were made into contralateral forelimb metacarpophalangeal joints, allowing researchers to compare the effects of both treatments within the same horse.
  • Clinical symptoms were evaluated, including both subjective and objective lameness, response to flexion, joint circumference, etc. Furthermore, arthrocentesis was performed to assess several cellular and protein-related variables.
  • These parameters were measured at multiple time points: before the treatment and 6, 12, 24, 72, 168, and 336 hours afterward.

Findings

  • The researchers noted no significant differences in any of the measured parameters between the joints that received autologous or allogeneic BMDMSCs.
  • The authors clarified that their study was not designed to assess the effectiveness of BMDMSCs for treating musculoskeletal diseases, which would require separate controlled trials.

Conclusion

  • The study concluded that there were no noticeable differences in joint responses to autologous or allogeneic BMDMSCs in the tested normal horses.
  • The authors suggested a larger study to confirm their findings and indicated that allogeneic BMDMSCs could potentially be a practical alternative to autologous BMDMSCs.

Cite This Article

APA
Colbath AC, Dow SW, Hopkins LS, Phillips JN, McIlwraith CW, Goodrich LR. (2019). Allogeneic vs. autologous intra-articular mesenchymal stem cell injection within normal horses: Clinical and cytological comparisons suggest safety. Equine Vet J, 52(1), 144-151. https://doi.org/10.1111/evj.13136

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 52
Issue: 1
Pages: 144-151

Researcher Affiliations

Colbath, A C
  • Orthopaedic Research Center, Colorado State University, School of Veterinary Medicine, Fort Collins, Colorado, USA.
Dow, S W
  • Department of Clinical Sciences, Colorado State University, School of Veterinary Medicine, Fort Collins, Colorado, USA.
Hopkins, L S
  • Department of Clinical Sciences, Colorado State University, School of Veterinary Medicine, Fort Collins, Colorado, USA.
Phillips, J N
  • Orthopaedic Research Center, Colorado State University, School of Veterinary Medicine, Fort Collins, Colorado, USA.
McIlwraith, C W
  • Orthopaedic Research Center, Colorado State University, School of Veterinary Medicine, Fort Collins, Colorado, USA.
Goodrich, L R
  • Orthopaedic Research Center, Colorado State University, School of Veterinary Medicine, Fort Collins, Colorado, USA.
  • Department of Clinical Sciences, Colorado State University, School of Veterinary Medicine, Fort Collins, Colorado, USA.

MeSH Terms

  • Animals
  • Biomarkers / chemistry
  • Bone Marrow Cells
  • Horses
  • Injections, Intra-Articular
  • Mesenchymal Stem Cell Transplantation / adverse effects
  • Mesenchymal Stem Cell Transplantation / veterinary
  • Mesenchymal Stem Cells / physiology
  • Synovial Fluid
  • Transplantation, Autologous
  • Transplantation, Homologous

Grant Funding

  • Wayne and Nancy McIlwraith Fellowship
  • Grayson Jockey Club Research Foundation
  • NIH Research Service Award

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