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Equine veterinary journal2013; 45(6); 726-731; doi: 10.1111/evj.12063

Distribution and persistence of technetium-99 hexamethyl propylene amine oxime-labelled bone marrow-derived mesenchymal stem cells in experimentally induced tendon lesions after intratendinous injection and regional perfusion of the equine distal limb.

Abstract: Intralesional (i.l.) injection is currently the most commonly used technique for stem cell therapy in equine tendon injury. A comparison of different techniques of injection of mesenchymal stem cells for the treatment of tendon lesions is required. Objective: We hypothesised that vascular perfusion of the equine distal limb with mesenchymal stem cells (MSCs) would result in preferential distribution of MSCs to acute tendon injuries. Methods: In vivo experimental study. Methods: Lesions were surgically induced in forelimb superficial digital flexor tendons of 8 horses. Three or 10 days after lesion induction, technetium-99 hexamethyl propylene amine oxime-labelled MSCs were injected via i.v. or intra-arterial (i.a.) regional limb perfusion (RLP) at the level of the distal antebrachium and compared to i.l. injection. Mesenchymal stem cell persistence and distribution within the forelimb and tendon lesions was assessed with scintigraphy for 24 h. Results: Lesion uptake was higher with i.l. injection than with RLP, but MSC persistence decreased similarly over time in all 3 techniques. Intra-arterial RLP resulted in a better distribution of MSCs and a higher uptake at the lesion site than i.v. RLP. Limbs perfused i.a. on Day 10 showed greater accumulation of MSCs in the lesion than limbs perfused on Day 3. Arterial thrombosis occurred in 50% of the i.v. RLP limbs and in 100% of the i.a. RLP limbs, which led to clinical complications in one horse. Conclusions: Compared with i.l. injection, RLP results in lower uptake but similar persistence of MSCs at the site of tendon lesions. A time dependent accumulation of MSCs was identified with i.a. RLP. The i.a. RLP appears more advantageous than the i.v. RLP in terms of distribution and uptake. However, the described i.a. technique produced arterial thrombosis and thus cannot currently be recommended for clinical use.
Publication Date: 2013-04-09 PubMed ID: 23574488DOI: 10.1111/evj.12063Google Scholar: Lookup
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  • Clinical Trial
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research article investigates the distribution and persistence of bone marrow-derived mesenchymal stem cells (MSCs) in tendon lesions in horses. The team compared different techniques for the injection of MSCs and hypothesized that vascular perfusion of the lower limb would lead to a higher concentration of MSCs in acute injuries. While the intralesional (i.l.) injection technique saw a higher initial uptake, its persistence decreased at similar rates across all methods. A time-dependent accumulation was found with intra-arterial regional limb perfusion (i.a. RLP).

Objective and Hypothesis

  • The article’s objective is to study the efficiency of the different methods of injecting mesenchymal stem cells (MSCs) into tendon lesions, particularly comparing intratendinous injection and limb perfusion in horses.
  • The hypothesis was that vascular perfusion of the distal limb in horses with MSCs would result in a more concentrated distribution of MSCs in acute tendon injuries.

Methodology

  • An experimental study was conducted in vivo, meaning within the living body of the horse.
  • Lesions were surgically induced in the superficial digital flexor tendons of the forelimbs of 8 horses. Three or 10 days after the lesion induction, MSCs labelled with technetium-99 hexamethyl propylene amine oxime were injected into the horses in three ways: intravenous or intra-arterial regional limb perfusion at the level of the distal antebrachium, and intratendinous injection.
  • The persistence and distribution of MSCs within the forelimb and tendon lesions were assessed using scintigraphy, a diagnostic test that allows for imaging of the inside of the body, for 24 hours following the procedures.

Results

  • Higher initial uptake was observed with direct injections into the lesion as compared to regional limb perfusion (RLP), however, the persistence of MSCs declined at similar rates across all three techniques.
  • The intra-arterial RLP technique resulted in more evenly distributed MSCs and a higher uptake at the lesion site compared to intravenous RLP.
  • When the limb was perfused intra-arterially on the tenth day, a greater accumulation of MSCs in the lesion was observed than when perfused on the third day.
  • However, arterial thrombosis (blood clots) occurred with both intra-arterial and intravenous RLP, leading to clinical complications in one of the horses in the experiment.

Conclusion

  • The article concludes that while RLP showed lower uptake than direct lesion injection, the two techniques exhibited similar persistence of MSCs at the lesion site.
  • The scientists identified a time-dependent accumulation of MSCs with the use of intra-arterial RLP, although complications occurred such as arterial blood clots.
  • It was concluded that the intra-arterial RLP method has advantages over the intravenous RLP method in terms of distribution and uptake, but due to the risk of arterial thrombosis, it cannot currently be suggested for clinical use.

Cite This Article

APA
Sole A, Spriet M, Padgett KA, Vaughan B, Galuppo LD, Borjesson DL, Wisner ER, Vidal MA. (2013). Distribution and persistence of technetium-99 hexamethyl propylene amine oxime-labelled bone marrow-derived mesenchymal stem cells in experimentally induced tendon lesions after intratendinous injection and regional perfusion of the equine distal limb. Equine Vet J, 45(6), 726-731. https://doi.org/10.1111/evj.12063

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 45
Issue: 6
Pages: 726-731

Researcher Affiliations

Sole, A
  • Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, USA.
Spriet, M
    Padgett, K A
      Vaughan, B
        Galuppo, L D
          Borjesson, D L
            Wisner, E R
              Vidal, M A

                MeSH Terms

                • Animals
                • Female
                • Forelimb
                • Horse Diseases / diagnostic imaging
                • Horse Diseases / therapy
                • Horses
                • Macrophages / metabolism
                • Male
                • Mesenchymal Stem Cell Transplantation / veterinary
                • Radionuclide Imaging / veterinary
                • Technetium Tc 99m Exametazime / pharmacology
                • Tendon Injuries / diagnostic imaging
                • Tendon Injuries / therapy
                • Ultrasonography

                Citations

                This article has been cited 21 times.