title: Therapeutic Mechanisms of Human Adipose-Derived Mesenchymal Stem Cells in a Rat Tendon Injury Model.
abstract: BACKGROUND
  Although survival of transplanted stem cells in vivo and differentiation of stem cells into tenocytes in vitro have been reported, there have been no in vivo studies demonstrating that mesenchymal stem cells (MSCs) could secrete their own proteins as differentiated tenogenic cells. Purpose/Hypothesis: Using a xenogeneic MSC transplantation model, we aimed to investigate whether MSCs could differentiate into the tenogenic lineage and secrete their own proteins. The hypothesis was that human MSCs would differentiate into the human tenogenic lineage and the cells would be able to secrete human-specific proteins in a rat tendon injury model.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  The Achilles tendons of 57 Sprague Dawley rats received full-thickness rectangular defects. After the modeling, the defective tendons were randomly assigned to 3 groups: (1) cell group, implantation with human adipose-derived mesenchymal stem cells (hASCs) and fibrin glue (106cells in 60 μL); (2) fibrin group, implantation with fibrin glue and same volume of cell media; and (3) sham group, identical surgical procedure without any treatment. Gross observation and biomechanical, histopathological, immunohistochemistry, and Western blot analyses were performed at 2 and 4 weeks after modeling.
  
  
  RESULTS
  hASCs implanted into the defective rat tendons were viable for 4 weeks as detected by immunofluorescence staining. Tendons treated with hASCs showed better gross morphological and biomechanical recovery than those in the fibrin and sham groups. Furthermore, the expression of both human-specific collagen type I and tenascin-C was significantly higher in the cell group than in the other 2 groups.
  
  
  CONCLUSIONS
  Transplantation of hASCs enhanced rat tendon healing biomechanically. hASCs implanted into the rat tendon defect model survived for at least 4 weeks and secreted human-specific collagen type I and tenascin-C. These findings suggest that transplanted MSCs may be able to differentiate into the tenogenic lineage and contribute their own proteins to tendon healing.
  
  
  CONCLUSIONS
  In tendon injury, MSCs can enhance tendon healing by secreting their own protein and have potential as a therapeutic option in human tendinopathy.
authors.affiliation: Department of Physical Medicine & Rehabilitation, Chung-Ang University College of Medicine, Seoul, South Korea.|Department of Rehabilitation Medicine, Seoul National University Boramae Medical Center, Seoul, South Korea.
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Bomi
authors.initials: B
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Kyoungbun
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Son
authors.affiliation: Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul, South Korea.|Institute of Aging, Seoul National University, Seoul, South Korea.|Rheumatism Research Institute, Medical Research Center, Seoul National University, Seoul, South Korea.
authors.forename: Sun G
authors.initials: SG
authors.lastname: Chung
mesh_terms: D000125:Achilles Tendon / Q000293:injuries; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D024042:Collagen Type I / Q000096:biosynthesis; D004195:Disease Models, Animal; D015718:Fibrin Tissue Adhesive / Q000008:administration & dosage; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D019063:Tenascin / Q000096:biosynthesis; D013708:Tendon Injuries / Q000378:metabolism / Q000628:therapy*; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; D015718:Fibrin Tissue Adhesive; D019063:Tenascin
keywords: Achilles tendon; collagen type I; mesenchymal stem cells; tendon injuries; xenogeneic stem cell transplantation