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Bone Marrow-Derived Mesenchymal Stem Cells Influence Early Tendon-Healing in a Rabbit Achilles Tendon Model
Alphonsus K.S. Chong, MBBS, MRCS, MMed1; Abel D. Ang, BSc1; James C.H. Goh, PhD1; James H.P. Hui, MBBS, FRCS1; Aymeric Y.T. Lim, MBBS, FRCS1; Eng Hin Lee, MD, FRCS(C)1; Beng Hai Lim, MBBS, FRCS1
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@gmail.com
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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.
Investigation performed at the National University Hospital and Yong Loo Lin School of Medicine, National University of Singapore, Singapore

The Journal of Bone and Joint Surgery, Incorporated
J Bone Joint Surg Am, 2007 Jan 01;89(1):74-81. doi: 10.2106/JBJS.E.01396
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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.

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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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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