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PloS one2014; 9(1); e85917; doi: 10.1371/journal.pone.0085917

Regenerative therapies for equine degenerative joint disease: a preliminary study.

Abstract: Degenerative joint disease (DJD) is a major cause of reduced athletic function and retirement in equine performers. For this reason, regenerative therapies for DJD have gained increasing interest. Platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) were isolated from a 6-year-old donor horse. MSCs were either used in their native state or after chondrogenic induction. In an initial study, 20 horses with naturally occurring DJD in the fetlock joint were divided in 4 groups and injected with the following: 1) PRP; 2) MSCs; 3) MSCs and PRP; or 4) chondrogenic induced MSCs and PRP. The horses were then evaluated by means of a clinical scoring system after 6 weeks (T1), 12 weeks (T2), 6 months (T3) and 12 months (T4) post injection. In a second study, 30 horses with the same medical background were randomly assigned to one of the two combination therapies and evaluated at T1. The protein expression profile of native MSCs was found to be negative for major histocompatibility (MHC) II and p63, low in MHC I and positive for Ki67, collagen type II (Col II) and Vimentin. Chondrogenic induction resulted in increased mRNA expression of aggrecan, Col II and cartilage oligomeric matrix protein (COMP) as well as in increased protein expression of p63 and glycosaminoglycan, but in decreased protein expression of Ki67. The combined use of PRP and MSCs significantly improved the functionality and sustainability of damaged joints from 6 weeks until 12 months after treatment, compared to PRP treatment alone. The highest short-term clinical evolution scores were obtained with chondrogenic induced MSCs and PRP. This study reports successful in vitro chondrogenic induction of equine MSCs. In vivo application of (induced) MSCs together with PRP in horses suffering from DJD in the fetlock joint resulted in a significant clinical improvement until 12 months after treatment.
Publication Date: 2014-01-20 PubMed ID: 24465787PubMed Central: PMC3896436DOI: 10.1371/journal.pone.0085917Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article is about a preliminary study conducted to evaluate the effectiveness of regenerative therapies, including platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs), in treating degenerative joint disease (DJD) in horses. The results showed significant clinical improvement in the treated horses, especially when both PRP and induced MSCs were used.

About Degenerative Joint Disease and Regenerative Therapies

  • DJD is a common disease in horses that often leads to decreased athletic performance and premature retirement. It involves deterioration of the joints, causing pain and functional impairment.
  • Regenerative therapies have emerged as a potential treatment for DJD. Among these therapies, PRP and MSCs have garnered significant interest.
  • PRP is a blood plasma that has been enriched with platelets. When injected into damaged tissues, PRP can potentially speed up healing.
  • MSCs are a type of stem cell capable of differentiating into a variety of cell types, including those that make up the cartilage in joints. Developers of the therapy hope that injecting MSCs into a damaged joint will encourage the development of new, healthy cartilage.

Details of the Study

  • The research involved two studies. The first included 20 horses with naturally occurring DJD. They were divided into four groups and received injections of PRP, MSCs, a combination of both, or a combination of PRP and MSCs that had been induced to become cartilage-producing cells.
  • The horses were then monitored over a period of 12 months. Assessments were made at 6 weeks, 12 weeks, 6 months, and 12 months following the injection. The researchers used a clinical scoring system to evaluate the condition of the horses.
  • In the second study, 30 additional horses with DJD were randomly assigned to one of the two combination therapies and evaluated 6 weeks (T1) after treatment.

Study Findings

  • The researchers found that the protein expression profile of native MSCs was negative for major histocompatibility (MHC) II and p63, low in MHC I, and positive for Ki67, Collagen type II, and Vimentin.
  • Chondrogenic induction of MSCs resulted in increased mRNA expression of aggrecan, Collagen II, and cartilage oligomeric matrix protein (COMP) along with an increase in protein expression of p63 and glycosaminoglycan (a component of cartilage) but a decrease in the protein expression of Ki67.
  • The combined use of PRP and MSCs significantly improved the functionality and sustainability of damaged joints from 6 weeks up to 12 months following treatment, compared to using PRP alone.
  • The best short-term clinical evolution scores were obtained with chondrogenic induced MSCs combined with PRP.

Conclusion

  • The study reports successful in vitro chondrogenic induction of equine MSCs. When applied in vivo (in the horse), these induced MSCs, along with PRP, resulted in significant clinical improvement in horses suffering from DJD.
  • This preliminary study provides a basis for future research and potential approval of MSC and PRP combination therapy for equine DJD.

Cite This Article

APA
Broeckx S, Zimmerman M, Crocetti S, Suls M, Mariën T, Ferguson SJ, Chiers K, Duchateau L, Franco-Obregón A, Wuertz K, Spaas JH. (2014). Regenerative therapies for equine degenerative joint disease: a preliminary study. PLoS One, 9(1), e85917. https://doi.org/10.1371/journal.pone.0085917

Publication

ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 9
Issue: 1
Pages: e85917

Researcher Affiliations

Broeckx, Sarah
  • Global Stem cell Technology, Meldert-Lummen, Belgium.
Zimmerman, Marieke
  • Equine Veterinary Practice Dr Suls, Weert, The Netherlands.
Crocetti, Sara
  • Department for Biomechanics, ETH Zurich, Zurich, Switzerland.
Suls, Marc
  • Equine Veterinary Practice Dr Suls, Weert, The Netherlands.
Mariën, Tom
  • Equitom Equine Hospital, Meldert-Lummen, Belgium.
Ferguson, Stephen J
  • Department for Biomechanics, ETH Zurich, Zurich, Switzerland ; Competence Center for Applied Biotechnology and Molecular Medicine CABMM, University of Zurich, Zurich, Switzerland.
Chiers, Koen
  • Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Duchateau, Luc
  • Department of Comparative Physiology and Biometrics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Franco-Obregón, Alfredo
  • Department for Biomechanics, ETH Zurich, Zurich, Switzerland ; Competence Center for Applied Biotechnology and Molecular Medicine CABMM, University of Zurich, Zurich, Switzerland ; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Wuertz, Karin
  • Department for Biomechanics, ETH Zurich, Zurich, Switzerland ; Competence Center for Applied Biotechnology and Molecular Medicine CABMM, University of Zurich, Zurich, Switzerland.
Spaas, Jan H
  • Global Stem cell Technology, Meldert-Lummen, Belgium.

MeSH Terms

  • Aggrecans / metabolism
  • Animals
  • Cell Differentiation
  • Chondrogenesis / physiology
  • Collagen Type II / metabolism
  • Horses
  • Joint Diseases / metabolism
  • Joint Diseases / therapy
  • Joint Diseases / veterinary
  • Male
  • Mesenchymal Stem Cell Transplantation / methods
  • Mesenchymal Stem Cell Transplantation / veterinary
  • Platelet-Rich Plasma / metabolism
  • Treatment Outcome

Conflict of Interest Statement

Competing Interests: The authors MS, TM and JHS declare competing financial interests as shareholders in Global Stem cell Technology (GST). SB and JHS are both employed by GST and inventors of several pending patents owned by GST (PCT/EP2013/070247, PCT/EP2013/070257 and PCT/EP2013/075782). The content of this manuscript contains products under development owned by GST. This does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials.

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