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Bone Marrow-Derived Mesenchymal Stem Cells Influence Early Tendon-Healing in a Rabbit Achilles Tendon Model

¹ Department of Hand and Reconstructive Microsurgery, National University Hospital (A.K.S.C. and A.Y.T.L.) and Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore (A.D.A., J.C.H.G., J.H.P.H., A.Y.T.L., E.H.L., and B.H.L.), 5 Lower Kent Ridge Road, Singapore 119074. E-mail address for A.K.S. Chong: alfchong{at}gmail.com

Investigation performed at the National University Hospital and Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Disclosure: In support of their research for or preparation of this manuscript, one or more of the authors received grants or outside funding from the National Medical Research Council, Singapore (NMRC 0751/2003 and NMRC 0894/2004). None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

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.

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.

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