Stem Cells Genetically Modified With the Developmental Gene MT1-MMP Improve Regeneration of the Supraspinatus Tendon-to-Bone Insertion Site

Hospital for Special Surgery, Sports Medicine/Shoulder Service, 535 E 70th Street, New York, NY 10021, USA.
The American Journal of Sports Medicine (Impact Factor: 4.36). 07/2010; 38(7):1429-37. DOI: 10.1177/0363546510361235
Source: PubMed


Rotator cuffs heal through a scar tissue interface after repair, which makes them prone to failure. Membrane type 1 matrix metalloproteinase (MT1-MMP) is upregulated during embryogenesis in areas that develop into tendon-bone insertion sites.
Bone marrow-derived stem cells in the presence of the developmental signal from MT1-MMP will drive the healing process toward regeneration and away from scar formation.
Controlled laboratory study.
Sixty Lewis rats underwent unilateral detachment and repair of the supraspinatus tendon. Thirty animals received mesenchymal stem cells (MSCs) in a fibrin glue carrier, and 30 received adenoviral MT1-MMP (Ad-MT1-MMP)-transduced MSCs. Animals were sacrificed at 2 weeks and 4 weeks and evaluated for the presence of fibrocartilage and collagen fiber organization at the insertion. Biomechanical testing was performed to determine the structural and material properties of the repaired tissue. Statistical analysis was performed with a Wilcoxon rank-sum test with significance set at P = .05.
There were no differences between the Ad-MT1-MMP and MSC groups in any outcome variable at 2 weeks. At 4 weeks, the Ad-MT1-MMP group had more fibrocartilage (P = .05), higher ultimate load to failure (P = .01), higher ultimate stress to failure (P = .005), and higher stiffness values (P = .02) as compared with the MSC group.
Mesenchymal stem cells genetically modified to overexpress the developmental gene MT1-MMP can augment rotator cuff healing at 4 weeks by the presence of more fibrocartilage at the insertion and improved biomechanical strength.
Biologic augmentation of repaired rotator cuffs with MT1-MMP-transduced MSCs may reduce the incidence of retears. However, further studies are needed to determine if this remains safe and effective in larger models.

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Available from: David Kovacevic, Nov 20, 2014
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    • "Knowledge of the biological signaling events that lead to the formation of the natural enthesis suggests candidate molecules that could be used in combination with MSCs to augment the repair site. Therefore, in later studies, Gulotta et al. [63, 64] examined various types of transduced MSCs with the aim of driving the healing process toward regeneration rather than repair of the tendon-bone structure. Three controlled laboratory studies showed that transducing cells with scleraxis or membrane type 1 matrix metalloproteinase improved histological quality and biomechanical strength as early as 4 weeks after repair, whereas transducing the cells with BMP-13 did not achieve favorable results. "
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