Background: A repaired tendon needs to be protected for weeks until
it has accrued enough strength to handle physiological loads.
Tissue-engineering techniques have shown promise in the treatment of tendon
and ligament defects. The present study tested the hypothesis that bone
marrow-derived mesenchymal stem cells can accelerate tendon-healing after
primary repair of a tendon injury in a rabbit model.
Methods: Fifty-seven New Zealand White rabbits were used as the
experimental animals, and seven others were used as the source of bone
marrow-derived mesenchymal stem cells. The injury model was a sharp complete
transection through the midsubstance of the Achilles tendon. The transected
tendon was immediately repaired with use of a modified Kessler suture and a
running epitendinous suture. Both limbs were used, and each side was
randomized to receive either bone marrow-derived mesenchymal stem cells in a
fibrin carrier or fibrin carrier alone (control). Postoperatively, the rabbits
were not immobilized. Specimens were harvested at one, three, six, and twelve
weeks for analysis, which included evaluation of gross morphology (sixty-two
specimens), cell tracing (twelve specimens), histological assessment (forty
specimens), immunohistochemistry studies (thirty specimens), morphometric
analysis (forty specimens), and mechanical testing (sixty-two specimens).
Results: There were no differences between the two groups with
regard to the gross morphology of the tendons. The fibrin had degraded by
three weeks. Cell tracing showed that labeled bone marrow-derived mesenchymal
stem cells remained viable and present in the intratendinous region for at
least six weeks, becoming more diffuse at later time-periods. At three weeks,
collagen fibers appeared more organized and there were better morphometric
nuclear parameters in the treatment group (p < 0.05). At six and twelve
weeks, there were no differences between the groups with regard to
morphometric nuclear parameters. Biomechanical testing showed improved modulus
in the treatment group as compared with the control group at three weeks (p
< 0.05) but not at subsequent time-periods.
Conclusions: Intratendinous cell therapy with bone marrow-derived
mesenchymal stem cells following primary tendon repair can improve
histological and biomechanical parameters in the early stages of
Clinical Relevance: The findings of the present study have clinical
importance as the early time-period during tendon-healing is crucial in the
treatment of tendon injuries.