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Stem cell research & therapy2011; 2(1); 4; doi: 10.1186/scrt45

Fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model.

Abstract: Tendon injury is a common problem in athletes, with poor tissue regeneration and a high rate of re-injury. Stem cell therapy is an attractive treatment modality as it may induce tissue regeneration rather than tissue repair. Currently, there are no reports on the use of pluripotent cells in a large animal tendon model in vivo. We report the use of intra-lesional injection of male, fetal derived embryonic-like stem cells (fdESC) that express Oct-4, Nanog, SSEA4, Tra 1-60, Tra 1-81 and telomerase. Methods: Tendon injury was induced using a collagenase gel-physical defect model in the mid-metacarpal region of the superficial digital flexor tendon (SDFT) of eight female adult Thoroughbred or Thoroughbred cross horses. Tendon lesions were treated one week later with intra-lesional injection of male derived fdESCs in media or media alone. Therapy was blinded and randomized. Serial ultrasound examinations were performed and final analysis at eight weeks included magnetic resonance imaging (MRI), biochemical assays (total DNA, glycosaminoglycan, collagen), gene expression (TNC, TNMD, SCX, COL1A1, COL3A1, COMP, DCN, MMP1, MMP3, MMP13, 18S) and histology. Differences between groups were assessed with Wilcoxon's rank sum test. Results: Cell survival was demonstrated via the presence of the SRY gene in fdESC treated, but not control treated, female SDFT at the end of the trial. There were no differences in tendon matrix specific gene expression or total proteoglycan, collagen or DNA of tendon lesions between groups. Tissue architecture, tendon size, tendon lesion size, and tendon linear fiber pattern were significantly improved on histologic sections and ultrasound in the fdESC treated tendons. Conclusions: Such profound structural effects lend further support to the notion that pluripotent stem cells can effect musculoskeletal regeneration, rather than repair, even without in vitro lineage specific differentiation. Further investigation into the safety of pluripotent cellular therapy as well as the mechanisms by which repair was improved seem warranted.
Publication Date: 2011-01-27 PubMed ID: 21272343PubMed Central: PMC3092144DOI: 10.1186/scrt45Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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 explores the use of fetal derived embryonic-like stem cells to enhance the healing of tendon injuries in large animals, particularly horses. The research found that these stem cells offer considerable promise in regenerating rather than merely repairing damaged tendons.

Research Methodology

  • The study applies a tendon injury model using collagenase gel-physical defect in adult Thoroughbred or Thoroughbred cross horses. The model created a controllable mid-metacarpal tendon injury in the superficial digital flexor tendon (SDFT).
  • Seven days after inducing the injury, an intra-lesional injection of male-derived fetal embryonic-like stem cells (fdESC) suspended in a medium, denoted as the treatment, was administered in the tendon lesions.
  • The study used a blinded and randomized therapy process to avoid any inadvertent bias.
  • Regular ultrasound examinations were performed to monitor the progress in the healing of injuries. A final examination at eight weeks involved a range of tests including magnetic resonance imaging (MRI), gene expression tests, biochemical assays, and histology.

Research Findings

  • The presence of the SRY gene in fdESC treated samples confirmed cell survival, which was absent in the control samples. However, no significant differences were found in the tendon matrix’s specific gene expression or proteoglycan, collagen, or DNA of tendon lesions between the treated and control groups.
  • Significant improvements were noticed in tissue architecture, tendon size, tendon lesion size, and tendon linear fiber pattern in the treated tendons both on histologic sections and through ultrasound imaging.

Conclusions and Implications

  • The results of this study support the idea that pluripotent stem cells can facilitate musculoskeletal regeneration beyond mere repair, even without the need for in vitro lineage-specific differentiation.
  • Given these promising findings, the research team recommends further investigations into the safety parameters of pluripotent cellular therapy and the exact mechanisms that brought about improved repair.

Cite This Article

APA
Watts AE, Yeager AE, Kopyov OV, Nixon AJ. (2011). Fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model. Stem Cell Res Ther, 2(1), 4. https://doi.org/10.1186/scrt45

Publication

ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 2
Issue: 1
Pages: 4

Researcher Affiliations

Watts, Ashlee E
  • Department of Clinical Sciences, Comparative Orthopaedics Laboratory at Cornell University, Ithaca, NY, 14850 USA. ajn1@cornell.edu
Yeager, Amy E
    Kopyov, Oleg V
      Nixon, Alan J

        MeSH Terms

        • Animals
        • Collagen / genetics
        • Collagen / immunology
        • Collagen / metabolism
        • DNA / metabolism
        • Disease Models, Animal
        • Female
        • Horse Diseases / diagnostic imaging
        • Horse Diseases / pathology
        • Horse Diseases / therapy
        • Horses
        • Magnetic Resonance Imaging
        • Male
        • Proteoglycans / genetics
        • Proteoglycans / metabolism
        • Regenerative Medicine
        • Sex-Determining Region Y Protein / genetics
        • Sex-Determining Region Y Protein / metabolism
        • Stem Cell Transplantation / veterinary
        • Stem Cells / cytology
        • Tendon Injuries / diagnostic imaging
        • Tendon Injuries / therapy
        • Tendon Injuries / veterinary
        • Ultrasonography
        • Wound Healing

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