title: Comparison of the efficacy of bone marrow mononuclear cells and bone mesenchymal stem cells in the treatment of osteoarthritis in a sheep model.
abstract: OBJECTIVE
  To evaluate the therapeutic efficacy of uncultured bone marrow mononuclear cells (BMMCs) and bone mesenchymal stem cells in an osteoarthritis (OA) model of sheep.
  
  
  METHODS
  Induction of sheep OA was performed surgically through anterior cruciate ligament transection and medial meniscectomy. After 12 weeks, concentrated BMMCs obtained from autologous bone marrow harvested from anterior iliac crest or a single dose of 10 million autologous bone mesenchymal stem cells (BMSCs) suspended in phosphate-buffered saline (PBS) was delivered to the injured knee via direct intra-articular injection. Animals of the PBS group received vehicle alone. The contra-lateral joints were selected randomly as the control group. Knees of the four groups were compared macroscopically and histologically, and glycosaminoglycan (GAG) contents normalized to cartilage wet weight were measured at lesions of cartilage from medial condyle of the femur head. Gene expression levels of type II collagen (Col2A1), Aggrecan and matrix metalloproteinase-13 (MMP-13) in cartilage were measured based on RT-PCR and prostaglandin E2 (PGE2), Tumor Necrosis Factor-α (TNF-α) and Transforming Growth Factor beta (TGF-β) concentrations in synovial fluid were determined with ELISA assays at 8 weeks after injection.
  
  
  RESULTS
  At 8 weeks post cell transplantation, partial cartilage repair was observed in the cell therapy, but not the PBS group (P<0.05). The BMSCs group showed higher regeneration of cartilage and lower proteoglycan loss than the BMMCs group (P<0.05). Concentrated BMMCs injection led to a weaker treatment effect, but also inhibited PGE2, TNF-α and TGF-β levels in synovial fluid and promoted higher levels of Aggrecan and Col2A1 and downregulation of MMP-13 in sheep chondrocytes in a similar manner to BMSCs, compared with the PBS group.
  
  
  CONCLUSIONS
  Bone marrow cells showed therapeutic efficacy in a sheep model of OA. Despite similar therapeutic potential, the easier and faster process of collection and isolation of BMMCs supports their utility as an effective alternative for OA treatment in the clinic.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University Nanjing, 210029, China.
authors.forename: Fanglong
authors.initials: F
authors.lastname: Song
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University Nanjing, 210029, China.
authors.forename: Jilei
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University Nanjing, 210029, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Geng
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University Nanjing, 210029, China.
authors.forename: Hansheng
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University Nanjing, 210029, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University Nanjing, 210029, China.
authors.forename: Weiding
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University Nanjing, 210029, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Fan
mesh_terms: D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D016026:Bone Marrow Transplantation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D024043:Collagen Type II / Q000378:metabolism; D004195:Disease Models, Animal; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D020370:Osteoarthritis, Knee / Q000209:etiology / Q000378:metabolism / Q000601:surgery*; D012756:Sheep; D016896:Treatment Outcome
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D053509:Matrix Metalloproteinase 13
keywords: Mesenchymal stem cells; OA; bone marrow mononuclear cells; sheep; treatment