Bone marrow-derived mesenchymal stem cells influence early tendon-healing in a rabbit achilles tendon model.
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 tendon-healing.
Chong
Alphonsus K S
AK
Department of Hand and Reconstructive Microsurgery, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074. alfchong@gmail.com
Ang
Abel D
AD
Goh
James C H
JC
Hui
James H P
JH
Lim
Aymeric Y T
AY
Lee
Eng Hin
EH
Lim
Beng Hai
BH
D000125:Achilles Tendon / Q000166:cytology / Q000293:injuries*; D000818:Animals; D001854:Bone Marrow Cells; D004195:Disease Models, Animal; D005260:Female; D015718:Fibrin Tissue Adhesive; D045164:Mesenchymal Stem Cell Transplantation; D011817:Rabbits; D013536:Suture Techniques; D013708:Tendon Injuries / Q000628:therapy; D023822:Tissue Engineering; D014945:Wound Healing / Q000502:physiology*
D015718:Fibrin Tissue Adhesive