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Distribution of injected technetium(99m)-labeled mesenchymal stem cells in horses with naturally occurring tendinopathy.

Abstract: This study aimed to investigate immediate cell survival and distribution following different administration routes of mesenchymal stem cells (MSCs) into naturally occurring tendon injuries. Ten million MSCs, labeled with technetium-99m hexamethylpropyleneamine oxime, were implanted into 13 horses with naturally occurring tendon or ligament injuries intra-lesionally, intravenously and by regional perfusion, and traced for up to 48 h using planar gamma scintigraphy. Labeling efficiencies varied between 1.8% and 18.5% (mean 9.3%). Cells were retained in the damaged area after intra-lesional administration but only 24% of cells were still present within the tendon after 24 h. After intravenous injection, cells largely distributed to the lung fields, with no detectable cells in the tendon lesions. Significant labeling of the tendon lesions was observed in 11/12 horses following regional perfusion but at a lower level to intra-lesional injection. The highest cell numbers were retained after intra-lesional injection, although with considerable cell loss, while regional perfusion may be a viable alternative for MSC delivery. Cells did not "home" to damaged tendon in large numbers after intravenous administration. Cells were detected in the lungs most frequently after intravascular administration, although with no adverse effects. Low cell retention has important implications for designing effective clinical therapies for human clinical use.
Publication Date: 2013-03-18 PubMed ID: 23508674DOI: 10.1002/jor.22338Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research investigates how effectively mesenchymal stem cells (MSCs), used for treating tendon and ligament injuries in horses, survive and distribute via different administration routes. The best method was found to be local injection at the injury site even though a considerable number of cells were lost; intravenous injection did not lead to significant cell accumulation at the injury site.

Objective of the research

  • The study sought to investigate how immediate cell survival and distribution varies with different routes of stem cell administration in naturally occurring tendon injuries. It aimed to determine the proportion of MSCs that remain at the lesion site and elsewhere in the body after intra-lesional, intravenous, and regional perfusion administration methods.

Methodology

  • The researchers injected 10 million MSCs, labeled with technetium-99m (Tc99m) hexamethylpropyleneamine oxime, into 13 horses suffering from tendon or ligament injuries through three different routes.
  • The distribution and survival of the cells were monitored up to 48 hours after the injection using gamma scintigraphy, a form of imaging used to examine the inside of the body’s functionality.

Results

  • The labeling efficiencies of Tc99m varied between 1.8% and 18.5% with an average of 9.3%.
  • When the stem cells were injected directly into the damaged area (intra-lesional administration), cells were retained in that area. However, 24 hours post-injection, only about 24% of the cells remained within the tendon.
  • Following intravenous administration, the cells were majorly distributed to the lung fields with no detectable cells found in the tendon lesions.
  • Regional perfusion resulted in significant labeling of the tendon lesions in 11 out of 12 horses but at a lower level than with the intra-lesional injection.
  • The intra-lesional injection retained the highest number of cells despite the considerable cell loss, making it the preferred MSC delivery method according to this study. Conversely, the efficiency of cell retention after regional perfusion suggests it as an available alternative for MSC delivery.

Implications and conclusion

  • The cells did not “home,” i.e. move towards the injured tendon in large numbers when administered intravenously.
  • The lungs appeared to be the most common site for cell accumulation following intravenous administration, but without causing adverse effects.
  • The study’s findings on low cell retention, especially with the intravenous and regional perfusion administration methods, create implications for designing more effective clinical therapies. Such therapies could potentially benefit not only veterinary medicine but also human clinical application, especially for tendon or ligament injury treatment.

Cite This Article

APA
Becerra P, Valdés Vázquez MA, Dudhia J, Fiske-Jackson AR, Neves F, Hartman NG, Smith RK. (2013). Distribution of injected technetium(99m)-labeled mesenchymal stem cells in horses with naturally occurring tendinopathy. J Orthop Res, 31(7), 1096-1102. https://doi.org/10.1002/jor.22338

Publication

ISSN: 1554-527X
NlmUniqueID: 8404726
Country: United States
Language: English
Volume: 31
Issue: 7
Pages: 1096-1102

Researcher Affiliations

Becerra, Patricia
  • Hospital de Referencia La Equina, Apdo 110, Camino de Martagina Km 1, Manilva-Málaga, 29692, Spain.
Valdés Vázquez, Miguel A
    Dudhia, Jayesh
      Fiske-Jackson, Andrew R
        Neves, Francisco
          Hartman, Neil G
            Smith, Roger K W

              MeSH Terms

              • Animals
              • Cells, Cultured
              • Female
              • Horse Diseases / pathology
              • Horse Diseases / therapy
              • Horses
              • Injections, Intralesional
              • Injections, Intravenous
              • Male
              • Mesenchymal Stem Cell Transplantation / methods
              • Mesenchymal Stem Cells / cytology
              • Mesenchymal Stem Cells / metabolism
              • Radionuclide Imaging
              • Technetium / metabolism
              • Tendinopathy / pathology
              • Tendinopathy / therapy
              • Tendinopathy / veterinary
              • Tendon Injuries / pathology
              • Tendon Injuries / therapy
              • Tendon Injuries / veterinary
              • Tendons / cytology
              • Tendons / metabolism
              • Time Factors
              • Treatment Outcome

              Citations

              This article has been cited 26 times.