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PloS one2013; 8(9); e75697; doi: 10.1371/journal.pone.0075697

Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy.

Abstract: Tendon injuries are a common age-related degenerative condition where current treatment strategies fail to restore functionality and normal quality of life. This disease also occurs naturally in horses, with many similarities to human tendinopathy making it an ideal large animal model for human disease. Regenerative approaches are increasingly used to improve outcome involving mesenchymal stem cells (MSCs), supported by clinical data where injection of autologous bone marrow derived MSCs (BM-MSCs) suspended in marrow supernatant into injured tendons has halved the re-injury rate in racehorses. We hypothesized that stem cell therapy induces a matrix more closely resembling normal tendon than the fibrous scar tissue formed by natural repair. Twelve horses with career-ending naturally-occurring superficial digital flexor tendon injury were allocated randomly to treatment and control groups. 1X10(7) autologous BM-MSCs suspended in 2 ml of marrow supernatant were implanted into the damaged tendon of the treated group. The control group received the same volume of saline. Following a 6 month exercise programme horses were euthanized and tendons assessed for structural stiffness by non-destructive mechanical testing and for morphological and molecular composition. BM-MSC treated tendons exhibited statistically significant improvements in key parameters compared to saline-injected control tendons towards that of normal tendons and those in the contralateral limbs. Specifically, treated tendons had lower structural stiffness (p<0.05) although no significant difference in calculated modulus of elasticity, lower (improved) histological scoring of organisation (p<0.003) and crimp pattern (p<0.05), lower cellularity (p<0.007), DNA content (p<0.05), vascularity (p<0.03), water content (p<0.05), GAG content (p<0.05), and MMP-13 activity (p<0.02). Treatment with autologous MSCs in marrow supernatant therefore provides significant benefits compared to untreated tendon repair in enhancing normalisation of biomechanical, morphological, and compositional parameters. These data in natural disease, with no adverse findings, support the use of this treatment for human tendon injuries.
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Publication Date: 2013-09-25 PubMed ID: 24086616PubMed Central: PMC3783421DOI: 10.1371/journal.pone.0075697Google Scholar: Lookup
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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 investigates the use of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in treating tendon injuries and reports promising outcomes, showing that the treatment can significantly aid in normalising biomechanical, morphological, and compositional parameters.

Understanding the problem

  • Tendon injuries, as the study notes, are age-related degenerative conditions which are marked by a challenging recovery and a severe impact on the sufferers’ quality of life.
  • The traditional treatment methods often fall short of fully restoring the functionality of the affected areas.
  • The study mentions the occurrence of similar conditions in horses, which makes them an ideal model for studying these diseases.

Regenerative approaches with MSCs

  • Regenerative therapies, particularly the application of mesenchymal stem cells (MSCs), offer some optimism. The effectiveness of MSCs has been corroborated by clinical data that show a significant reduction in the re-injury rate among racehorses treated with MSCs.
  • The researchers speculate that stem cell therapy could lead to the formation of a matrix resembling the normal tendon rather than allowing the fibrous scar tissue produced by the natural repair process to form.

The experimental procedure

  • The scientists worked with horses with career-ending tendon injuries, dividing them into control and experiment groups.
  • The experiment group was treated with autologous BM-MSCs suspended in marrow supernatant, while the control group was given saline instead.
  • After a 6-month exercise period, the horses were euthanized and the tendons assessed for various parameters including structure, morphology and molecular composition.

Observations and conclusions

  • The conclusion was that tendons treated with BM-MSCs demonstrated significant improvement in numerous aspects, edging closer to the characteristics of normal tendons.
  • The parameters that exhibited improved scores included structural stiffness, histological scoring of organisation and crimp pattern, cellularity, DNA content, vascularity, water content, GAG content, and MMP-13 activity.
  • In conclusion, the researchers suggest that the use of autologous MSCs in marrow supernatant allows for substantial benefits towards tendon repair. It aids biomechanical, morphological, and compositional normalization.
  • This indicates that this form of therapy could potentially be effective in treating human tendon injuries.

Cite This Article

APA
Smith RK, Werling NJ, Dakin SG, Alam R, Goodship AE, Dudhia J. (2013). Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy. PLoS One, 8(9), e75697. https://doi.org/10.1371/journal.pone.0075697

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 8
Issue: 9
Pages: e75697

Researcher Affiliations

Smith, Roger Kenneth Whealands
  • Department of Clinical Sciences and Services, the Royal Veterinary College, University of London, Hatfield, United Kingdom.
Werling, Natalie Jayne
    Dakin, Stephanie Georgina
      Alam, Rafiqul
        Goodship, Allen E
          Dudhia, Jayesh

            MeSH Terms

            • Animals
            • Bone Marrow / physiology
            • Cell- and Tissue-Based Therapy / methods
            • Horse Diseases / physiopathology
            • Horse Diseases / therapy
            • Horses
            • Mesenchymal Stem Cells / physiology
            • Physical Conditioning, Animal / physiology
            • Tendinopathy / physiopathology
            • Tendinopathy / therapy
            • Tendinopathy / veterinary
            • Tendon Injuries / physiopathology
            • Tendon Injuries / therapy
            • Tendon Injuries / veterinary
            • Tendons / physiology
            • Wound Healing / physiology

            Conflict of Interest Statement

            Competing Interests: The authors have the following interests. This study was partly funded by VetCell Bioscience Ltd. RKS was a director of VetCell Bioscience Ltd, UK from 2002 - 2010. There are no patents, products in development or marketed products to declare. This does not alter their adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

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