Application of bone marrow-derived mesenchymal stem cells in a rotator cuff repair model

Lawrence V Gulotta, David Kovacevic, John R Ehteshami, Elias Dagher, Jonathan D Packer, Scott A Rodeo
American Journal of Sports Medicine 2009, 37 (11): 2126-33

BACKGROUND: Rotator cuff tendons heal to bone with interposed scar tissue, which makes repairs prone to failure. The purpose of this study was to determine if the application of bone marrow-derived mesenchymal stem cells (MSCs) can improve rotator cuff healing after repair.

HYPOTHESIS: Application of MSCs to the repair site will result in superior results compared with controls on histologic and biomechanical testing.

STUDY DESIGN: Controlled laboratory study.

METHODS: Ninety-eight Lewis rats underwent unilateral detachment and repair of the supraspinatus tendon; 10 rats were used for MSC harvest. Eight animals were used for cell tracking with Ad-LacZ. The remaining animals received either 10(6) MSCs in a fibrin carrier, the carrier alone, or nothing at the repair site. Animals were sacrificed at 2 and 4 weeks for histologic analysis to determine the amount of fibrocartilage formation and the collagen organization at the insertion. Biomechanical testing was also performed.

RESULTS: Specimens treated with Ad-LacZ-transduced MSCs exhibited more beta-galactosidase activity at the repair site compared with controls at both 2 and 4 weeks, although activity at 4 weeks was less than that at 2 weeks. There were no differences in the amount of new cartilage formation or collagen fiber organization between groups at either time point. There were also no differences in the biomechanical strength of the repairs, the cross-sectional area, peak stress to failure, or stiffness.

CONCLUSION: The addition of MSCs to the healing rotator cuff insertion site did not improve the structure, composition, or strength of the healing tendon attachment site despite evidence that they are present and metabolically active.

CLINICAL RELEVANCE: A biologic solution to the problem of tendon-to-bone healing in the rotator cuff remains elusive. The repair site may lack the cellular and/or molecular signals necessary to induce appropriate differentiation of transplanted cells. Further studies are needed to determine if cell-based strategies need to be combined with growth and differentiation factors to be effective.

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