Equine allogeneic chondrogenic induced mesenchymal stem cells: A GCP target animal safety and biodistribution study.
Abstract: The safety of the intra-articular use of mesenchymal stem cells (MSCs) is scarcely reported. Therefore, the goal of this study was to investigate the safety of a single intra-articular injection with allogeneic chondrogenic induced MSCs combined with equine plasma (=the investigational product: IVP) compared to a saline (0.9% NaCl) placebo control (=control product: CP). Sixteen healthy experimental horses were randomly assigned to receive a single intra-articular injection with either the IVP (n=8) or the CP (n=8) in the left metacarpophalangeal joint. All horses underwent a daily clinical assessment throughout the entire study period of 42days to assess adverse events. Additionally, a local joint assessment and a lameness examination were performed daily during the first two weeks, and weekly the following 4weeks. Blood samples were taken weekly for hematological and biochemical analysis. At the end of the study period, horses of the IVP group were euthanized for a thorough necropsy and to check for biodistribution. Tissue samples of the injected joint were collected for histological examination. In both CP and IVP treated horses a mild transient subjective increase in periarticular temperature and lameness was noted after the intra-articular injection with no significant differences between the treatment groups. No distribution of the cells was found using immunohistochemistry and no ectopic tissue formation or signs of inflammation were found on histology. A single intra-articular injection of allogeneic chondrogenic induced MSCs combined with allogeneic plasma in horses had the same clinical side effects as an intra-articular injection with saline solution.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Publication Date: 2017-12-27 PubMed ID: 29329028DOI: 10.1016/j.rvsc.2017.12.018Google Scholar: Lookup
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- Clinical Trial
- Veterinary
- Journal Article
Summary
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This study researched the safety of injecting horses with allogeneic chondrogenic induced mesenchymal stem cells (MSCs) in combination with equine plasma, by comparing it to a saline solution. The outcome showed that it was a safe procedure with the same clinical side effects as an injection of saline solution and did not cause inflammation or distribution of cells.
Overview of the Study
- The researchers conducted a study on 16 healthy horses to examine the effects of injection with allogeneic chondrogenic induced MSCs. The horses were injected in the left metacarpophalangeal joint with either the investigational product (IVP) or the control product (CP).
- The IVP was a combination of MSCs and equine plasma, while the CP was a saline solution. The horses were randomly assigned to one of the two treatment groups.
- The horses were closely monitored for 42 days. Their day-to-day health, joint status, and any signs of lameness were assessed on a weekly basis, with blood samples also collected each week for analysis.
Post-Treatment Assessment and Findings
- At the end of the study period, the horses from the IVP group were euthanized and underwent an in-depth necropsy to check for biodistribution. Tissue samples were taken from the injected joint for histological examination.
- The findings showed a mild, temporary increase in periarticular temperature and lameness after injection in both IVP and CP-treated horses, indicating that there were no significant differences between the two groups in terms of side effects from the procedure.
- Immunohistochemistry and histology did not reveal any signs of inflammation or any distribution of cells, nor did they find any ectopic tissue formation.
Conclusions
- The study concludes that a single intra-articular injection of allogeneic chondrogenic induced MSCs combined with equine plasma in horses has the same clinical side effects as an intra-articular injection with saline solution.
- This implies the procedure was safe, and did not cause any problematic side effects or complications that distinguished it from a saline injection.
Cite This Article
APA
Broeckx SY, Spaas JH, Chiers K, Duchateau L, Van Hecke L, Van Brantegem L, Dumoulin M, Martens AM, Pille F.
(2017).
Equine allogeneic chondrogenic induced mesenchymal stem cells: A GCP target animal safety and biodistribution study.
Res Vet Sci, 117, 246-254.
https://doi.org/10.1016/j.rvsc.2017.12.018 Publication
Researcher Affiliations
- Global Stem Cell Technology NV, Anacura Group, Noorwegenstraat 4, 9940 Evergem, Belgium.
- Global Stem Cell Technology NV, Anacura Group, Noorwegenstraat 4, 9940 Evergem, Belgium.
- Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
- Biometrics Research Group, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
- Biometrics Research Group, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. Electronic address: Lore.Vanhecke@anacura.com.
- Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
- Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
- Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
- Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
MeSH Terms
- Animals
- Chondrogenesis
- Horses
- Injections, Intra-Articular / veterinary
- Joint Diseases / therapy
- Joint Diseases / veterinary
- Mesenchymal Stem Cells
- Tissue Distribution
Citations
This article has been cited 10 times.- Mayet A, Zablotski Y, Roth SP, Brehm W, Troillet A. Systematic review and meta-analysis of positive long-term effects after intra-articular administration of orthobiologic therapeutics in horses with naturally occurring osteoarthritis. Front Vet Sci 2023;10:1125695.
- Supokawej A, Korchunjit W, Wongtawan T. The combination of BMP12 and KY02111 enhances tendon differentiation in bone marrow-derived equine mesenchymal stromal cells (BM-eMSCs). J Equine Sci 2022 Jul;33(2):19-26.
- Depuydt E, Broeckx SY, Chiers K, Patruno M, Da Dalt L, Duchateau L, Saunders J, Pille F, Martens A, Van Hecke L, Spaas JH. Cellular and Humoral Immunogenicity Investigation of Single and Repeated Allogeneic Tenogenic Primed Mesenchymal Stem Cell Treatments in Horses Suffering From Tendon Injuries. Front Vet Sci 2021;8:789293.
- Colbath AC, Dow SW, Hopkins LS, Phillips JN, McIlwraith CW, Goodrich LR. 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 2020 Jul;52(4):601-612.
- Magri C, Schramme M, Febre M, Cauvin E, Labadie F, Saulnier N, François I, Lechartier A, Aebischer D, Moncelet AS, Maddens S. Comparison of efficacy and safety of single versus repeated intra-articular injection of allogeneic neonatal mesenchymal stem cells for treatment of osteoarthritis of the metacarpophalangeal/metatarsophalangeal joint in horses: A clinical pilot study. PLoS One 2019;14(8):e0221317.
- Daems R, Van Hecke L, Schwarzkopf I, Depuydt E, Broeckx SY, David M, Beerts C, Vandekerckhove P, Spaas JH. A Feasibility Study on the Use of Equine Chondrogenic Induced Mesenchymal Stem Cells as a Treatment for Natural Occurring Osteoarthritis in Dogs. Stem Cells Int 2019;2019:4587594.
- Bertoni L, Branly T, Jacquet S, Desancé M, Desquilbet L, Rivory P, Hartmann DJ, Denoix JM, Audigié F, Galéra P, Demoor M. Intra-Articular Injection of 2 Different Dosages of Autologous and Allogeneic Bone Marrow- and Umbilical Cord-Derived Mesenchymal Stem Cells Triggers a Variable Inflammatory Response of the Fetlock Joint on 12 Sound Experimental Horses. Stem Cells Int 2019;2019:9431894.
- Broeckx SY, Martens AM, Bertone AL, Van Brantegem L, Duchateau L, Van Hecke L, Dumoulin M, Oosterlinck M, Chiers K, Hussein H, Pille F, Spaas JH. The use of equine chondrogenic-induced mesenchymal stem cells as a treatment for osteoarthritis: A randomised, double-blinded, placebo-controlled proof-of-concept study. Equine Vet J 2019 Nov;51(6):787-794.
- Roffi A, Nakamura N, Sanchez M, Cucchiarini M, Filardo G. Injectable Systems for Intra-Articular Delivery of Mesenchymal Stromal Cells for Cartilage Treatment: A Systematic Review of Preclinical and Clinical Evidence. Int J Mol Sci 2018 Oct 25;19(11).
- Aeri A, Gorla M, Sharma GT. Veterinary Regenerative Medicine: The Evolving Role of Stem Cell-Based Therapies. Stem Cell Rev Rep 2025 Nov;21(8):2484-2510.
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