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Veterinary and comparative orthopaedics and traumatology : V.C.O.T2013; 26(6); 453-460; doi: 10.3415/VCOT-13-01-0008

Inflammatory effects of autologous, genetically modified autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses.

Abstract: To compare the clinical and inflammatory joint responses to intra-articular injection of bone marrow-derived mesenchymal stem cells (MSC) including autologous, genetically modified autologous, allogeneic, or xenogeneic cells in horses. Methods: Six five-year-old Thoroughbred mares had one fetlock joint injected with Gey's balanced salt solution as the vehicle control. Each fetlock joint of each horse was subsequently injected with 15 million MSC from the described MSC groups, and were assessed for 28 days for clinical and inflammatory parameters representing synovitis, joint swelling, and pain. Results: There were not any significant differences between autologous and genetically modified autologous MSC for synovial fluid total nucleated cell count, total protein, interleukin (IL)-6, IL-10, fetlock circumference, oedema score, pain-free range-of-motion, and soluble gene products that were detected for at least two days. Allogeneic and xenogeneic MSC produced a greater increase in peak of inflammation at 24 hours than either autologous MSC group. Conclusions: Genetically engineered MSC can act as vehicles to deliver gene products to the joint; further investigation into the therapeutic potential of this cell therapy is warranted. Intra-articular MSC injection resulted in a moderate acute inflammatory joint response that was greater for allogeneic and xenogeneic MSC than autologous MSC. Clinical management of this response may minimize this effect.
Publication Date: 2013-10-01 PubMed ID: 24080668DOI: 10.3415/VCOT-13-01-0008Google Scholar: Lookup
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  • Controlled Clinical Trial
  • Journal Article

Summary

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This research compared the effects of injecting different types of mesenchymal stem cells (MSCs) – specifically autologous (from the same individual), genetically modified autologous, allogeneic (from a different individual of the same species), and xenogeneic (from a different species) – into horse joints. They found that the inflammation response was greater when using allogeneic and xenogeneic MSCs, and suggest further research into the therapeutic potential of genetically engineered MSCs.

Research Design and Methodology

  • The subjects of this study were six Thoroughbred mares (female horses), all five years old. The selection of a single breed and age group helped to establish a controlled environment, minimizing potential age or breed-specific variations.
  • The researchers injected one fetlock joint (a joint located in the horse’s leg) with Gey’s balanced salt solution as a control measure, to compare the effects of the different stem cell types.
  • Different categories of MSCs were injected into each horse’s fetlock joint, and the horses were monitored for 28 days for various clinical and inflammatory parameters, which provide indicators of inflammation, swelling, and pain in the joint.

Study Findings

  • As per the results, no significant differences were observed between the effects of autologous and genetically modified autologous MSCs, suggesting that the genetic modification didn’t notably alter the cells’ impact on inflammation or swelling.
  • Allogeneic and xenogeneic MSCs produced an noticeably increased inflammatory response 24 hours after injection compared to either autologous MSC group.
  • Gene products were also detected up to two days post-injection in the joints where genetically engineered MSCs were used, indicating that these can be used to deliver gene products to a targeted area.

Conclusions and Implications

  • The researchers concluded that genetically engineered MSCs show promise as a means of delivering gene products to targeted areas. If they can effectively reduce inflammation and pain, they may offer a potential therapy for conditions affecting the joints.
  • However, this study found that using allogeneic and xenogeneic MSCs induced a greater inflammatory response, which has implications for their use in clinical practice. Strategies to manage this response would be necessary to minimize potential adverse effects.

Cite This Article

APA
Pigott JH, Ishihara A, Wellman ML, Russell DS, Bertone AL. (2013). Inflammatory effects of autologous, genetically modified autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses. Vet Comp Orthop Traumatol, 26(6), 453-460. https://doi.org/10.3415/VCOT-13-01-0008

Publication

ISSN: 2567-6911
NlmUniqueID: 8906319
Country: Germany
Language: English
Volume: 26
Issue: 6
Pages: 453-460

Researcher Affiliations

Pigott, J H
  • Dr. Alicia L. Bertone, DVM, PhD, Department of Veterinary Clinical Sciences, The Ohio State University, 380 VMAB, 1900 Coffey Rd, Columbus, OH 43210, United States, Phone: +1 614 292 6661, Fax: +1 614 688 5642, E-mail: bertone.1@osu.edu.
Ishihara, A
    Wellman, M L
      Russell, D S
        Bertone, A L

          MeSH Terms

          • Animals
          • Bone Morphogenetic Protein 2 / genetics
          • Bone Morphogenetic Protein 2 / metabolism
          • Female
          • Gene Expression Regulation
          • Genetic Engineering
          • Horse Diseases / therapy
          • Horses
          • Inflammation / etiology
          • Inflammation / veterinary
          • Injections, Intra-Articular
          • Mesenchymal Stem Cell Transplantation / adverse effects
          • Mesenchymal Stem Cell Transplantation / methods
          • Mesenchymal Stem Cell Transplantation / veterinary
          • Mesenchymal Stem Cells / classification
          • Osteoarthritis / therapy
          • Osteoarthritis / veterinary
          • Synovial Fluid / chemistry
          • Synovial Fluid / cytology

          Citations

          This article has been cited 22 times.