title: Cartilage matrix formation by bovine mesenchymal stem cells in three-dimensional culture is age-dependent.
abstract: BACKGROUND
  Cartilage degeneration is common in the aged, and aged chondrocytes are inferior to juvenile chondrocytes in producing cartilage-specific extracellular matrix. Mesenchymal stem cells (MSCs) are an alternative cell type that can differentiate toward the chondrocyte phenotype. Aging may influence MSC chondrogenesis but remains less well studied, particularly in the bovine system.
  
  
  OBJECTIVE
  The objectives of this study were (1) to confirm age-related changes in bovine articular cartilage, establish how age affects chondrogenesis in cultured pellets for (2) chondrocytes and (3) MSCs, and (4) determine age-related changes in the biochemical and biomechanical development of clinically relevant MSC-seeded hydrogels.
  
  
  METHODS
  Native bovine articular cartilage from fetal (n = 3 donors), juvenile (n = 3 donors), and adult (n = 3 donors) animals was analyzed for mechanical and biochemical properties (n = 3-5 per donor). Chondrocyte and MSC pellets (n = 3 donors per age) were cultured for 6 weeks before analysis of biochemical content (n = 3 per donor). Bone marrow-derived MSCs of each age were also cultured within hyaluronic acid hydrogels for 3 weeks and analyzed for matrix deposition and mechanical properties (n = 4 per age).
  
  
  RESULTS
  Articular cartilage mechanical properties and collagen content increased with age. We observed robust matrix accumulation in three-dimensional pellet culture by fetal chondrocytes with diminished collagen-forming capacity in adult chondrocytes. Chondrogenic induction of MSCs was greater in fetal and juvenile cell pellets. Likewise, fetal and juvenile MSCs in hydrogels imparted greater matrix and mechanical properties.
  
  
  CONCLUSIONS
  Donor age and biochemical microenvironment were major determinants of both bovine chondrocyte and MSC functional capacity.
  
  
  CONCLUSIONS
  In vitro model systems should be evaluated in the context of age-related changes and should be benchmarked against human MSC data.
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, 424 Stemmler Hall, 36th Street and Hamilton Walk, Philadelphia, PA 19104, USA.
authors.forename: Isaac E
authors.initials: IE
authors.lastname: Erickson
authors.forename: Steven C
authors.initials: SC
authors.lastname: van Veen
authors.forename: Swarnali
authors.initials: S
authors.lastname: Sengupta
authors.forename: Sydney R
authors.initials: SR
authors.lastname: Kestle
authors.forename: Robert L
authors.initials: RL
authors.lastname: Mauck
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D001696:Biomechanical Phenomena; D002356:Cartilage / Q000378:metabolism* / Q000637:transplantation; D002417:Cattle; D002454:Cell Differentiation; D002478:Cells, Cultured; D016922:Cellular Senescence; D019902:Chondrocytes / Q000378:metabolism* / Q000637:transplantation; D020219:Chondrogenesis; D003094:Collagen / Q000096:biosynthesis; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006820:Hyaluronic Acid / Q000737:chemistry; D020100:Hydrogels; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D046509:Tissue Culture Techniques; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D006025:Glycosaminoglycans; D020100:Hydrogels; D006820:Hyaluronic Acid; D003094:Collagen