title: Mesenchymal stem cells from a hypoxic culture improve and engraft Achilles tendon repair.
abstract: BACKGROUND
  Bone marrow-derived mesenchymal stem cells (MSCs) from humans cultured under hypoxic conditions increase bone healing capacity.
  
  
  OBJECTIVE
  Rat MSCs cultured under hypoxic conditions increase the tendon healing potential after transplantation into injured Achilles tendons.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  Biomechanical testing, histological analysis, and bromodeoxyuridine (BrdU) labeling/collagen immunohistochemistry were performed to demonstrate that augmentation of an Achilles tendon rupture site with hypoxic MSCs increases healing capacity compared with normoxic MSCs and controls. Fifty Sprague-Dawley rats were used for the experiments, with 2 rats as the source of bone marrow MSCs. The cut Achilles tendons in the rats were equally divided into 3 groups: hypoxic MSC, normoxic MSC, and nontreated (vehicle control). The uncut tendons served as normal uncut controls. Outcome measures included mechanical testing in 24 rats, histological analysis, and BrdU labeling/collagen immunohistochemistry in another 24 rats.
  
  
  RESULTS
  The ultimate failure load in the hypoxic MSC group was significantly greater than that in the nontreated or normoxic MSC group at 2 weeks after incision (2.1 N/mm(2) vs 1.1 N/mm(2) or 1.9 N/mm(2), respectively) and at 4 weeks after incision (5.5 N/mm(2) vs 1.7 N/mm(2) or 2.7 N/mm(2), respectively). The ultimate failure load in the hypoxic MSC group at 4 weeks after incision (5.5 N/mm(2)) was close to but still significantly less than that of the uncut tendon (7.2 N/mm(2)). Histological analysis as determined by the semiquantitative Bonar histopathological grading scale revealed that the hypoxic MSC group underwent a significant improvement in Achilles tendon healing both at 2 and 4 weeks when compared with the nontreated or normoxic MSC group via statistical analysis. Immunohistochemistry further demonstrated that the hypoxic and normoxic MSC groups had stronger immunostaining for type I and type III collagen than did the nontreated group both at 2 and 4 weeks after incision. Moreover, BrdU labeling of MSCs before injection further determined the incorporation and retention of transplanted cells at the rupture site.
  
  
  CONCLUSIONS
  Transplantation of hypoxic MSCs may be a better and more readily available treatment than normoxic MSCs for Achilles tendon ruptures.
  
  
  CONCLUSIONS
  The present study provides evidence that transplantation of hypoxic MSCs may be a promising therapy for the treatment of Achilles tendon ruptures.
authors.affiliation: Department of Surgery, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Tung-Fu
authors.initials: TF
authors.lastname: Huang
authors.forename: Tu-Lai
authors.initials: TL
authors.lastname: Yew
authors.forename: En-Rung
authors.initials: ER
authors.lastname: Chiang
authors.forename: Hsiao-Li
authors.initials: HL
authors.lastname: Ma
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Hsu
authors.forename: Shan-Hui
authors.initials: SH
authors.lastname: Hsu
authors.forename: Yuan-Tong
authors.initials: YT
authors.lastname: Hsu
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Hung
mesh_terms: D000125:Achilles Tendon / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D046508:Culture Techniques; D005260:Female; D000860:Hypoxia; D045164:Mesenchymal Stem Cell Transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013314:Stress, Mechanical; D013312:Stress, Physiological; D013718:Tensile Strength; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III
keywords: Achilles tendon healing; collagen; hypoxic culture; marrow stromal cells; multipotent stromal cells