title: Bone marrow-derived mesenchymal stem cells transduced with scleraxis improve rotator cuff healing in a rat model.
abstract: BACKGROUND
  Rotator cuffs heal through a scar tissue interface after repair that makes them prone to failure. Scleraxis (Scx) is a basic helix-loop-helix transcription factor that is thought to direct tendon development during embryogenesis. The purpose of this study was to determine if the application of mesenchymal stem cells (MSCs) transduced with adenoviral-mediated scleraxis (Ad-Scx) could improve regeneration of the tendon-bone insertion site in a rat rotator cuff repair model.
  
  
  OBJECTIVE
  Bone marrow-derived cells transduced with Scx would improve the structure of the healing tendon-bone interface and result in increased tendon attachment strength.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  Sixty Lewis rats underwent unilateral detachment and repair of the supraspinatus tendon. Thirty animals received MSCs in a fibrin glue carrier, and 30 received Ad-Scx-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 Scx and MSC groups in terms of histologic appearance at 2 weeks. However, the Scx group had higher ultimate stress-to-failure (2.6 ± 0.9 vs 1.7 ± 0.3 MPa; P = .03) and stiffness (8.4 ± 2.9 vs 5.0 ± 1.9 N/mm; P = .01) compared with the MSC group. At 4 weeks, the Scx group had more fibrocartilage (728.7 ± 50.4 vs 342.6 ± 217.0 mm(2); P = .04), higher ultimate load to failure (26.7 ± 4.6 vs 20.8 ± 4.4 N; P = .01), higher ultimate stress to failure (4.7 ± 1.3 vs 3.5 ± 1.0 MPa; P < .04), and higher stiffness values (15.3 ± 3.4 vs 9.3 ± 2.2 N/mm; P < .001) as compared with the MSC group.
  
  
  CONCLUSIONS
  Mesenchymal stem cells genetically modified with Scx can augment rotator cuff healing at early time points.
  
  
  CONCLUSIONS
  Biologic augmentation of acutely injured rotator cuffs with Scx-transduced MSCs may improve rotator cuff tendon healing and reduce the incidence of re-tears. However, further studies are needed to determine if this remains safe and effective in larger models.
authors.affiliation: Hospital for Special Surgery, 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: Jonathan D
authors.initials: JD
authors.lastname: Packer
authors.forename: Xiang Hua
authors.initials: XH
authors.lastname: Deng
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rodeo
mesh_terms: D000256:Adenoviridae; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001696:Biomechanical Phenomena; D016026:Bone Marrow Transplantation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D045164:Mesenchymal Stem Cell Transplantation; D051381:Rats; D011917:Rats, Inbred Lew; D017006:Rotator Cuff / Q000473:pathology; D000070636:Rotator Cuff Injuries; D013708:Tendon Injuries / Q000473:pathology / Q000628:therapy*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C503815:Scx protein, mouse