title: Extracellular matrix components and culture regimen selectively regulate cartilage formation by self-assembling human mesenchymal stem cells in vitro and in vivo.
abstract: Cartilage formation from self-assembling mesenchymal stem cells (MSCs) in vitro recapitulate important cellular events during mesenchymal condensation that precedes native cartilage development. The goal of this study was to investigate the effects of cartilaginous extracellular matrix (ECM) components and culture regimen on cartilage formation by self-assembling human MSCs in vitro and in vivo.
  
  
  
  Human bone marrow-derived MSCs (hMSCs) were seeded and compacted in 6.5-mm-diameter transwell inserts with coated (type I, type II collagen) or uncoated (vehicle) membranes, at different densities (0.5 × 106, 1.0 × 106, 1.5 × 106per insert). Pellets were formed by aggregating hMSCs (0.25 × 106) in round-bottomed wells. All tissues were cultured for up to 6 weeks for in vitro analyses. Discs (cultured for 6, 8 or 10 weeks) and pellets (cultured for 10 weeks) were implanted subcutaneously in immunocompromised mice to evaluate the cartilage stability in vivo.
  
  
  
  Type I and type II collagen coatings enabled cartilage disc formation from self-assembling hMSCs. Without ECM coating, hMSCs formed dome-shaped tissues resembling the pellets. Type I collagen, expressed in the prechondrogenic mesenchyme, improved early chondrogenesis versus type II collagen. High seeding density improved cartilage tissue properties but resulted in a lower yield of disc formation. Discs and pellets exhibited compositional and organizational differences in vitro and in vivo. Prolonged chondrogenic induction of the discs in vitro expedited endochondral ossification in vivo.
  
  
  
  The outcomes of cartilage tissues formed from self-assembling MSCs in vitro and in vivo can be modulated by the control of culture parameters. These insights could motivate new directions for engineering cartilage and bone via a cartilage template from self-assembling MSCs.
authors.affiliation: Department of Biomedical Engineering, Columbia University, 622 West 168th Street, VC12-234, New York, NY, 10032, USA.
authors.forename: Johnathan
authors.initials: J
authors.lastname: Ng
authors.affiliation: Department of Biomedical Engineering, Columbia University, 622 West 168th Street, VC12-234, New York, NY, 10032, USA.
authors.forename: Yiyong
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Biomedical Engineering, Columbia University, 622 West 168th Street, VC12-234, New York, NY, 10032, USA.|Columbia University, 345 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY, 10027, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Biomedical Engineering, Columbia University, 622 West 168th Street, VC12-234, New York, NY, 10032, USA.
authors.forename: Aonnicha
authors.initials: A
authors.lastname: Burapachaisri
authors.affiliation: Department of Biomedical Engineering, Columbia University, 622 West 168th Street, VC12-234, New York, NY, 10032, USA.|Columbia University, 345 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY, 10027, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Guo
authors.affiliation: Department of Biomedical Engineering, Columbia University, 622 West 168th Street, VC12-234, New York, NY, 10032, USA. gv2131@columbia.edu.|Department of Medicine, Columbia University, New York, NY, USA. gv2131@columbia.edu.
authors.forename: Gordana
authors.identifier: 0000-0002-9382-1574
authors.initials: G
authors.lastname: Vunjak-Novakovic
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002356:Cartilage / Q000166:cytology* / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis / Q000502:physiology; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D016513:Mice, SCID; D010012:Osteogenesis / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods
chemical_list: D024042:Collagen Type I; D024043:Collagen Type II