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Cartilage2023; 19476035231209402; doi: 10.1177/19476035231209402

Integrin α10β1-Selected Mesenchymal Stem Cells Reduce Pain and Cartilage Degradation and Increase Immunomodulation in an Equine Osteoarthritis Model.

Abstract: Integrin α10β1-selected mesenchymal stem cells (integrin α10-MSCs) have previously shown potential in treating cartilage damage and osteoarthritis (OA) and in animal models . The aim of this study was to further investigate disease-modifying effects of integrin α10-MSCs. Methods: OA was surgically induced in 17 horses. Eighteen days after surgery, horses received 2 × 10 integrin α10-MSCs intra-articularly or were left untreated. Lameness and response to carpal flexion was assessed weekly along with synovial fluid (SF) analysis. On day 52 after treatment, horses were euthanized, and carpi were evaluated by computed tomography (CT), MRI, histology, and for macroscopic pathology and integrin α10-MSCs were traced in the joint tissues. Results: Lameness and response to carpal flexion significantly improved over time following integrin α10-MSC treatment. Treated horses had milder macroscopic cartilage pathology and lower cartilage histology scores than the untreated group. Prostaglandin E2 and interleukin-10 increased in the SF after integrin α10-MSC injection. Integrin α10-MSCs were found in SF from treated horses up to day 17 after treatment, and in the articular cartilage and subchondral bone from 5 of 8 treated horses after euthanasia at 52 days after treatment. The integrin α10-MSC injection did not cause joint flare. Conclusions: This study demonstrates that intra-articular (IA) injection of integrin α10-MSCs appears to be safe, alleviate pathological changes in the joint, and improve joint function in an equine post-traumatic osteoarthritis (PTOA) model. The results suggest that integrin α10-MSCs hold promise as a disease-modifying osteoarthritis drug (DMOAD).
Publication Date: 2023-11-21 PubMed ID: 37990503DOI: 10.1177/19476035231209402Google Scholar: Lookup
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  • Journal Article

Summary

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This research investigates the potential of a specific type of mesenchymal stem cells (MSCs) in treating osteoarthritis by alleviating pain, reducing cartilage damage, and increasing immunomodulation in horses. The results show improvements in horses treated with these MSCs, supporting their use as a future osteoarthritis treatment.

Research Methods

  • Osteoarthritis was surgically induced in 17 horses. After 18 days, horses were either untreated or received an injection of integrin α10β1-selected mesenchymal stem cells (integrin α10-MSCs), which had previously shown potential for treating osteoarthritis, into their joints.
  • Horses’ responses to joint stress and their lameness were monitored weekly alongside analyses of their synovial fluid (the fluid in their joints).
  • The horses were euthanized 52 days after treatment and their joints were evaluated through multiple means including computed tomography (CT), magnetic resonance imaging (MRI), and histology (microscopic evaluation of tissues).
  • The researchers traced the location of the injected integrin α10-MSCs in the joint tissues both during the treatment and after euthanasia.

Study Findings

  • The researchers observed a significant improvement in lameness and response to joint stress in the horses treated with integrin α10-MSCs, which suggests an alleviation of osteoarthritis symptoms.
  • Joints of the treated horses exhibited milder damage visible to the naked eye and lower scores of cartilage damage when evaluated microscopically in comparison to the untreated horses.
  • Two molecular markers of inflammation, prostaglandin E2 and interleukin-10, were found to have increased in the joint fluid after injection of integrin α10-MSCs, showing an immune response.
  • The integrin α10-MSCs were present the joint fluid up to 17 days post-treatment and in the articular cartilage and bone of some treated horses 52 days after treatment, showing their persistence in the joint.
  • No adverse reactions, such as inflammation in the joint (referred to as “joint flare”), were observed following integrin α10-MSC injection into the joint.

Study Conclusions

  • This study demonstrates that injecting integrin α10-MSCs into the joints appears to be safe, reduces pathological changes in the joint, and improves joint function in an equine model of post-traumatic osteoarthritis.
  • The results suggest that integrin α10-MSCs have potential as a disease-modifying drug for the treatment of osteoarthritis.

Cite This Article

APA
Andersen C, Jacobsen S, Uvebrant K, Griffin JF, Vonk LA, Walters M, Berg LC, Lundgren-Åkerlund E, Lindegaard C. (2023). Integrin α10β1-Selected Mesenchymal Stem Cells Reduce Pain and Cartilage Degradation and Increase Immunomodulation in an Equine Osteoarthritis Model. Cartilage, 19476035231209402. https://doi.org/10.1177/19476035231209402

Publication

ISSN: 1947-6043
NlmUniqueID: 101518378
Country: United States
Language: English
Pages: 19476035231209402

Researcher Affiliations

Andersen, Camilla
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
  • Xintela AB, Lund, Sweden.
Jacobsen, Stine
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Uvebrant, Kristina
  • Xintela AB, Lund, Sweden.
Griffin, John F
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, USA.
Vonk, Lucienne Angela
  • Xintela AB, Lund, Sweden.
Walters, Marie
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Berg, Lise Charlotte
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Lundgren-Åkerlund, Evy
  • Xintela AB, Lund, Sweden.
Lindegaard, Casper
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.

Conflict of Interest Statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: E.L.-Å. is the CEO and CSO of Xintela AB, holds stock in the company, and is an inventor of a patent related to this study. K.U. was an employee of and holds stock in Xintela AB. L.A.V was an employee of Xintela AB.

Citations

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