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The American journal of sports medicine2020; 48(3); 612-623; doi: 10.1177/0363546519899087

Integrin α10β1-Selected Mesenchymal Stem Cells Mitigate the Progression of Osteoarthritis in an Equine Talar Impact Model.

Abstract: Early intervention with mesenchymal stem cells (MSCs) after articular trauma has the potential to limit progression of focal lesions and prevent ongoing cartilage degeneration by modulating the joint environment and/or contributing to repair. Integrin α10β1 is the main collagen type II binding receptor on chondrocytes, and MSCs that are selected for high expression of the α10 subunit have improved chondrogenic potential. The ability of α10β1-selected (integrin α10high) MSCs to protect cartilage after injury has not been investigated. To investigate integrin α10high MSCs to prevent posttraumatic osteoarthritis in an equine model of impact-induced talar injury. Controlled laboratory study. Focal cartilage injuries were created on the tali of horses (2-5 years, n = 8) by using an impacting device equipped to measure impact stress. Joints were treated with 20 × 106 allogenic adipose-derived α10high MSCs or saline vehicle (control) 4 days after injury. Synovial fluid was collected serially and analyzed for protein content, cell counts, markers of inflammation (prostaglandin E2, tumor necrosis factor α) and collagen homeostasis (procollagen II C-propeptide, collagen type II cleavage product), and glycosaminoglycan content. Second-look arthroscopy was performed at 6 weeks, and horses were euthanized at 6 months. Joints were imaged with radiographs and quantitative 3-T magnetic resonance imaging. Postmortem examinations were performed, and India ink was applied to the talar articular surface to identify areas of cartilage fibrillation. Synovial membrane and osteochondral histology was performed, and immunohistochemistry was used to assess type I and II collagen and lubricin. A mixed effect model with Tukey post hoc and linear contrasts or paired t tests were used, as appropriate. Integrin α10high MSC-treated joints had less subchondral bone sclerosis on radiographs (P = .04) and histology (P = .006) and less cartilage fibrillation (P = .04) as compared with control joints. On gross pathology, less India ink adhered to impact sites in treated joints than in controls, which may be explained by the finding of more prominent lubricin immunostaining in treated joints. Prostaglandin E2 concentration in synovial fluid and mononuclear cell synovial infiltrate were increased in treated joints, suggesting possible immunomodulation by integrin α10high MSCs. Intra-articular administration of integrin α10high MSCs is safe, and evidence suggests that the cells mitigate the effects of joint trauma. This preclinical study indicates that intra-articular therapy with integrin α10high MSCs after joint trauma may be protective against posttraumatic osteoarthritis.
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Publication Date: 2020-01-31 PubMed ID: 32004077DOI: 10.1177/0363546519899087Google Scholar: Lookup
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  • Journal Article

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 article studies the use of mesenchymal stem cells (MSCs) with particular integrin “α10β1” to retard the progression of osteoarthritis in horses after joint trauma. The study concluded positively on the safety and potential effectiveness of the intra-articular administration of these stem cells to counter osteoarthritis post joint injury.

Research Background and Aim

  • The study was instigated due to a lack of existing research into whether integrin α10 MSCs can protect cartilage after injury and thereby prevent osteoarthritis.
  • The researchers aimed to explore these effects with a controlled laboratory experiment using an equine model of impact-induced talar injury.

Methodology

  • Controlled injuries were inflicted on the “tali” (ankle bone) of healthy horses aged 2-5 years using an impacting device.
  • After four days of inducing injury, the joints were either treated with allogenic adipose-derived α10 MSCs or a saline vehicle (control).
  • Synovial fluid was subsequently collected and examined for protein content, cell counts, inflammation level(NSAIDs, TNF), collagen homeostasis, and glycosaminoglycan content.
  • The procedures were followed by second-look arthroscopy at the six-week mark, and the horses were euthanized at the six-month mark for final postmortem examinations. This included imaging tests, histology, and immunohistochemistry for collagen type I and II, and lubricin.

Findings

  • Results demonstrated that integrin α10 MSC-treated joints showed less subchondral bone sclerosis and cartilage fibrillation compared to the control joints.
  • There was also less India ink adherence to the impact sites in treated joints, probably due to more apparent lubricin staining.
  • The study also found an increase in the concentration of Prostaglandin E2 in the synovial fluid and more mononuclear cell synovial infiltration, possibly indicating possible immunomodulation by integrin α10 MSCs.

Conclusion

  • The study concludes that the intra-articular administration of integrin α10 MSCs is safe.
  • Moreover, evidence suggests that these cells mitigate the effects of joint trauma, making this form of therapy potentially protective against posttraumatic osteoarthritis.

Cite This Article

APA
Delco ML, Goodale M, Talts JF, Pownder SL, Koff MF, Miller AD, Nixon B, Bonassar LJ, Lundgren-Åkerlund E, Fortier LA. (2020). Integrin α10β1-Selected Mesenchymal Stem Cells Mitigate the Progression of Osteoarthritis in an Equine Talar Impact Model. Am J Sports Med, 48(3), 612-623. https://doi.org/10.1177/0363546519899087

Publication

The American journal of sports medicine
ISSN: 1552-3365
NlmUniqueID: 7609541
Country: United States
Language: English
Volume: 48
Issue: 3
Pages: 612-623

Researcher Affiliations

Delco, Michelle L
  • Cornell University, Ithaca, New York, USA.
Goodale, Margaret
  • Cornell University, Ithaca, New York, USA.
Talts, Jan F
  • Xintela AB, Medicon Village, Lund, Sweden.
Pownder, Sarah L
  • Hospital for Special Surgery, New York, New York, USA.
Koff, Matthew F
  • Hospital for Special Surgery, New York, New York, USA.
Miller, Andrew D
  • Cornell University, Ithaca, New York, USA.
Nixon, Bridgette
  • Cornell University, Ithaca, New York, USA.
Bonassar, Lawrence J
  • Cornell University, Ithaca, New York, USA.
Lundgren-Åkerlund, Evy
  • Xintela AB, Medicon Village, Lund, Sweden.
Fortier, Lisa A
  • Cornell University, Ithaca, New York, USA.

MeSH Terms

  • Animals
  • Cartilage, Articular / metabolism
  • Cell Differentiation / physiology
  • Chondrocytes
  • Chondrogenesis / physiology
  • Horses
  • Integrins / metabolism
  • Mesenchymal Stem Cells / physiology
  • Osteoarthritis / therapy

Citations

This article has been cited 30 times.
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