The authors declare that they have no competing interests.
ER, PA, JK and BE conceived the project and designed the animal study. ER performed the experiments and analysed the data. ER, PA and BE evaluated the results. ER wrote the first draft of the manuscript. All authors provided feedback and comments on the manuscript. All authors read and approved the final version of the manuscript.
The recent discovery of residing tendon stem/progenitor cells has triggered a growing interest in stem cells as a useful tool in tendon repair. Our knowledge of their involvement in naturally healing tendons is, however, sparse. The aim of this study was to identify and determine stem/progenitor cells in relation to different healing phases and regions in a rat model of Achilles tendon rupture.
Surgery was performed to create a mid-tendon rupture on the right Achilles tendon of 24 rats, whereas the left tendon was used as a control. Tendons were harvested at one, two, eight and 17 weeks post-rupture and stained with antibodies specific to stem/progenitor cells (Octamer-binding transcription factor 3/4 (Oct 3/4) and nucleostemin), migrating cells (Dynamin 2 (Dyn 2)) and leukocytes (CD45). A histological examination was performed on sections stained with Alcian blue.
At one and two weeks post-rupture, a large number of stem/progenitor cells were discovered throughout the tendon. Most of these cells were nucleostemin positive, whereas only a few Oct 3/4-positive cells were found, mainly situated inside the injury region (I region). At eight and 17 weeks, the increment in stem/progenitor cells had diminished to equal that in the control tendons. At all time points, Oct 3/4-positive cells were also found in the connective tissue surrounding the tendon and at the muscle-tendon junction in both ruptured and control tendons and were often seen at the same location as the migration marker, Dyn 2.
The whole length of the Achilles tendon is infiltrated by stem/progenitor cells at early time points after a mid-tendon rupture. However, different stem/progenitor cell populations exhibit varying anatomical and temporal expressions during Achilles tendon healing, suggesting distinct reparative implications. Oct 3/4 may thus act as a more local, migrating stem/progenitor cell involved in injury-site-specific regenerative effects, as compared to the more general proliferative role of nucleostemin-positive stem/progenitor cells.
Ackermann PW, Hart DA. Influence of Comorbidities: Neuropathy, Vasculopathy, and Diabetes on Healing Response Quality. Adv Wound Care (New Rochelle). 2013;2:410–21. CrossRef
Archer C, Ralphs J. Regenerative Medicine And Biomaterials for the Repair Of Connective Tissue. Cambridge: Woodhead Publishing; 2010. CrossRef
Leadbetter WB. Cell-matrix response in tendon injury. Clin Sports Med. 1992;11:533–78. PubMed
Runesson E, Ackermann P, Brisby H, Karlsson J, Eriksson BI. Detection of slow-cycling and tendon stem/progenitor cells in different regions of rat Achilles tendon: response to treadmill exercise. Knee Surg, Sports Traumatol, Arthrosc. 2012;21:1694–703. CrossRef
Tsai RY, McKay RD. A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells. Genes & Development. 2002;16:2991–3003. CrossRef
Ackermann P. Peptidergic innervation of periarticular tissue-A study in the rat, PhD Thesis. Stockholm: Karolinska Institute; 2001.
Sharma P, Maffulli N. Biology of tendon injury: healing, modeling and remodeling. J Musculoskelet Neuronal Interact. 2006;6:181–90. PubMed
- Nucleostemin- and Oct 3/4-positive stem/progenitor cells exhibit disparate anatomical and temporal expression during rat Achilles tendon healing
Bengt I Eriksson
- BioMed Central
Neu im Fachgebiet Orthopädie und Unfallchirurgie
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