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Cell transplantation2016; 25(12); 2199-2211; doi: 10.3727/096368916X692104

Long-Term Cell Tracking Following Local Injection of Mesenchymal Stromal Cells in the Equine Model of Induced Tendon Disease.

Abstract: Tendon disease has been treated with multipotent mesenchymal stromal cells (MSCs) in the equine large-animal model with promising success. The aim of this study was to gain more insight into the fate and biodistribution of MSCs after local application into tendon lesions by long-term cell tracking in this large-animal model. Superficial digital flexor tendon lesions were induced in all limbs in six horses and injected with 10106 Molday ION Rhodamine B-labeled MSCs suspended in serum or serum alone. Follow-up was performed using low-field magnetic resonance imaging (MRI), flow cytometry, and histology. Cell tracking based on the hypointense artifacts induced by the superparamagnetic iron oxide (SPIO) labeling agent in MRI as well as based on Rhodamine B fluorescence was feasible. However, Prussian blue staining for assessment of histology was not entirely specific for SPIO. Labeled cells could be traced at their injection site by MRI as well as histology for the whole follow-up period of 24 weeks. Although the numbers of labeled cells within the injected tendon lesions decreased over time, part of the applied cells appeared to remain viable and integrated within the injured tissue. Furthermore, small numbers of labeled cells were identified in peripheral blood within the first 24 h after cell injection and could also be found until week 24 within the contralateral control tendon lesions that had been injected with serum. The present findings unveil details on MSC biodistribution and persistence after their local application, which are of clinical relevance with regard to MSC safety and mechanisms of action.
Publication Date: 2016-07-07 PubMed ID: 27392888DOI: 10.3727/096368916X692104Google Scholar: Lookup
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  • Journal Article

Summary

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This research paper describes a study investigating how mesenchymal stromal cells (MSCs), a type of stem cell, behave and distribute in the body over time after being injected into a horse’s tendon. The results offer insights on the safety and effectiveness of MSCs in treating tendon disease.

Methodology

  • The research involved six horses, each with induced superficial digital flexor tendon lesions in all limbs.
  • These lesions were injected either with MSCs labeled with Molday ION Rhodamine B, a fluorescence dye, and suspended in serum, or with serum alone as a control.
  • The research team used low-field magnetic resonance imaging (MRI), flow cytometry, and histology to track and monitor the cells in the horses over 24 weeks.

Observations

  • The cells were tracked based on hypointense artifacts seen in the MRI, which were induced by the superparamagnetic iron oxide (SPIO) labeling agent used. This was feasible for cell tracking; however, Prussian blue staining for histology assessment wasn’t entirely specific for SPIO.
  • The MSCs remained visible at the injection site for the entire 24-week follow-up period, both in the MRI scans and the histology. Despite the number of labeled cells decreasing over time, some cells appeared viable and fully integrated with the affected tissue.
  • Small amounts of labeled cells were found in the horse’s peripheral blood within the first 24 hours post-injection, and were detectable until the 24th week in the control tendon lesions that were only injected with serum.

Conclusion

This research provides further insight into the behavior and distribution of MSCs following local injection. The researchers concluded that these findings are significant in understanding the clinical safety and action mechanisms of MSCs, as they appear to remain viable and integrated within the affected tissues for extended periods. Further, they can migrate to other parts of the body, including peripheral blood and contralateral control tendon lesions. Therefore, these findings could have significant implications for the development of stem cell-based treatments for tendon disease in the future.

Cite This Article

APA
Burk J, Berner D, Brehm W, Hillmann A, Horstmeier C, Josten C, Paebst F, Rossi G, Schubert S, Ahrberg AB. (2016). Long-Term Cell Tracking Following Local Injection of Mesenchymal Stromal Cells in the Equine Model of Induced Tendon Disease. Cell Transplant, 25(12), 2199-2211. https://doi.org/10.3727/096368916X692104

Publication

ISSN: 1555-3892
NlmUniqueID: 9208854
Country: United States
Language: English
Volume: 25
Issue: 12
Pages: 2199-2211

Researcher Affiliations

Burk, Janina
    Berner, Dagmar
      Brehm, Walter
        Hillmann, Aline
          Horstmeier, Carolin
            Josten, Christoph
              Paebst, Felicitas
                Rossi, Giacomo
                  Schubert, Susanna
                    Ahrberg, Annette B

                      MeSH Terms

                      • Animals
                      • Cell Tracking / methods
                      • Cell- and Tissue-Based Therapy / methods
                      • Female
                      • Ferric Compounds / chemistry
                      • Flow Cytometry
                      • Horses
                      • Magnetic Resonance Imaging
                      • Male
                      • Mesenchymal Stem Cells / cytology
                      • Mesenchymal Stem Cells / physiology
                      • Rhodamines / chemistry
                      • Tendon Injuries / surgery
                      • Tendon Injuries / therapy
                      • Tendons / metabolism
                      • Tendons / pathology

                      Citations

                      This article has been cited 20 times.
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