title: Stem cells genetically modified with the developmental gene MT1-MMP improve regeneration of the supraspinatus tendon-to-bone insertion site.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hospital for Special Surgery, Sports Medicine/Shoulder Service, 535 E 70th Street, New York, NY 10021, USA. GulottaL@hss.edu
authors.forename: Lawrence V
authors.initials: LV
authors.lastname: Gulotta
authors.forename: David
authors.initials: D
authors.lastname: Kovacevic
authors.forename: Scott
authors.initials: S
authors.lastname: Montgomery
authors.forename: John R
authors.initials: JR
authors.lastname: Ehteshami
authors.forename: Jonathon D
authors.initials: JD
authors.lastname: Packer
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rodeo
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000517:prevention & control*; D015718:Fibrin Tissue Adhesive / Q000627:therapeutic use; D051445:Fibrocartilage / Q000601:surgery; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017006:Rotator Cuff / Q000502:physiology*; D013708:Tendon Injuries / Q000201:enzymology / Q000601:surgery*; D014161:Transduction, Genetic; D014945:Wound Healing / Q000235:genetics*
chemical_list: D015718:Fibrin Tissue Adhesive; D020781:Matrix Metalloproteinase 1