title: Reconstruction of cartilage with clonal mesenchymal stem cell-acellular dermal matrix in cartilage defect model in nonhuman primates.
abstract: OBJECTIVE
  Articular cartilage defects are commonly associated with trauma, inflammation and osteoarthritis. Mesenchymal stem cell (MSC)-based therapy is a promising novel approach for repairing articular cartilage. Direct intra-articular injection of uncommitted MSCs does not regenerate high-quality cartilage. This study explored utilization of a new three-dimensional, selected chondrogenic clonal MSC-loaded monkey acellular dermal matrix (MSC-ADM) scaffold to repair damaged cartilage in an experimental model of knee joint cartilage defect in Cynomolgus monkeys.
  
  
  METHODS
  MSCs were characterized for cell size, cell yield, phenotypes, proliferation and chondrogenic differentiation capacity. Chondrogenic differentiation assays were performed at different MSC passages by sulfated glycosaminoglycans (sGAG), collagen, and fluorescence activated cell sorter (FACS) analysis. Selected chondrogenic clonal MSCs were seeded onto ADM scaffold with the sandwich model and MSC-loaded ADM grafts were analyzed by confocal microscopy and scanning electron microscopy. Cartilage defects were treated with normal saline, clonal MSCs and clonal MSC-ADM grafts, respectively. The clinical parameters, and histological and immunohistochemical examinations were evaluated at weeks 8, 16, 24 post-treatment, respectively.
  
  
  RESULTS
  Polyclonal and clonal MSCs could differentiate into the chondrogenic lineage after stimulation with suitable chondrogenic factors. They expressed mesenchymal markers and were negative for hematopoietic markers. Articular cartilage defects were considerably improved and repaired by selected chondrogenic clonal MSC-based treatment, particularly, in MSC-ADM-treated group. The histological scores in MSC-ADM-treated group were consistently higher than those of other groups.
  
  
  CONCLUSIONS
  Our results suggest that selected chondrogenic clonal MSC-loaded ADM grafts could improve the cartilage lesions in Cynomolgus monkey model, which may be applicable for repairing similar human cartilage defects.
authors.affiliation: Department of Surgery, Research Center, CHUM (CRCHUM), Notre-Dame Hospital, University of Montreal, Montreal, Canada.
authors.forename: Anlun
authors.initials: A
authors.lastname: Ma
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Lijun
authors.initials: L
authors.lastname: Song
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Hu
authors.forename: Hao
authors.initials: H
authors.lastname: Dun
authors.forename: Pierre
authors.initials: P
authors.lastname: Daloze
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Yu
authors.forename: Jianyuan
authors.initials: J
authors.lastname: Jiang
authors.forename: Muhammad
authors.initials: M
authors.lastname: Zafarullah
authors.forename: Huifang
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000293:injuries / Q000473:pathology / Q000601:surgery*; D003114:Colony-Forming Units Assay; D007718:Knee Injuries / Q000473:pathology / Q000601:surgery*; D007719:Knee Joint / Q000473:pathology / Q000601:surgery*; D008252:Macaca fascicularis; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D012867:Skin / Q000166:cytology*