title: Efficacy and Safety of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Anterior Cruciate Ligament Reconstruction of a Rabbit Model: New Strategy to Enhance Tendon Graft Healing.
abstract: OBJECTIVE
  To investigate whether non-autologous transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) could be integrated safely at the bone-tendon junction without immune rejection and could enhance bone-tendon healing effectively during anterior cruciate ligament (ACL) reconstruction in an animal model.
  
  
  METHODS
  ACL reconstructions using hamstring tendons were performed in 30 adult rabbits. The bone tunnels were treated with hUCB-MSCs or were untreated. The specimens were harvested at 4, 8, and 12 weeks. We performed a gross examination of the knee joint; a histologic assessment using H&E staining, as well as immunohistochemical staining, for type II collagen; and an evaluation of bone tunnel widening using micro-computed tomography.
  
  
  RESULTS
  No evidence of immune rejection was detected. Tendon-bone healing through Sharpey-like fibers was noticed around tendon grafts at 12 weeks in the control group. A smooth transition from bone to tendon through broad fibrocartilage formation was identified in the treatment group, and the interface zone showed abundant type II collagen production on immunohistochemical staining. Histologic scores for bone-tendon healing were significantly higher in the treatment group at all time points (P < .001). Micro-computed tomography at 12 weeks showed a significantly smaller tibial (P = .029) and femoral (P = .033) bone tunnel enlargement in the treated group than in the control group.
  
  
  CONCLUSIONS
  Non-autologous transplantation of hUCB-MSCs was applied in ACL reconstruction without early immune rejection. There was enhanced tendon-bone healing through broad fibrocartilage formation with higher histologic scores and decreased femoral and tibial tunnel widening compared with the control group (79.2% and 80%, respectively, of the control group tunnel area at 12 weeks).
  
  
  CONCLUSIONS
  Non-autologous transplantation of hUCB-MSCs has therapeutic potential in promoting tendon-to-bone healing after ACL reconstruction. Further study in the human model is warranted.
authors.affiliation: Department of Orthopaedic Surgery, Anam Hospital, Korea University School of Medicine, Seoul, Republic of Korea.
authors.forename: Ki-Mo
authors.initials: KM
authors.lastname: Jang
authors.affiliation: Department of Orthopedic Surgery, Guro Hospital, Korea University School of Medicine, Seoul, Republic of Korea.
authors.forename: Hong Chul
authors.initials: HC
authors.lastname: Lim
authors.affiliation: Department of Pathology, Guro Hospital, Korea University School of Medicine, Seoul, Republic of Korea.
authors.forename: Woon Yong
authors.initials: WY
authors.lastname: Jung
authors.affiliation: Department of Orthopaedic Surgery, Inje University College of Medicine, Haeundae Paik Hospital, Busan, Republic of Korea.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Moon
authors.affiliation: Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: mdwang88@gmail.com.
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery*; D000070598:Anterior Cruciate Ligament Injuries; D059549:Anterior Cruciate Ligament Reconstruction / Q000379:methods*; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D011817:Rabbits; D013710:Tendons / Q000637:transplantation*; D016896:Treatment Outcome; D014945:Wound Healing; D055114:X-Ray Microtomography