title: Insulin-like growth factor I enhances collagen synthesis in engineered human tendon tissue.
abstract: OBJECTIVE
  Isolated human tendon cells form 3D tendon constructs that demonstrate collagen fibrillogenesis and feature structural similarities to tendon when cultured under tensile load. The exact role of circulating growth factors for collagen formation in tendon is sparsely examined. We investigated the influence of insulin-like growth factor I (IGF-I) on tendon construct formation in 3D cell culture.
  
  
  METHODS
  Tendon constructs were grown in 0.5 or 10% FBS with or without IGF-I (250 mg/ml) supplementation. Collagen content (fluorometric), mRNA levels (PCR) and fibril diameter (transmission electron microscopy) were determined at 7, 10, 14, 21 and 28 days.
  
  
  RESULTS
  IGF-I revealed a stimulating effect on fibril diameter (up to day 21), mRNA for collagen (to day 28), tenomodulin (to day 28) and scleraxis (at days 10 and 14), and on overall collagen content. 10% FBS diminished the development of fibril diameter (day 14), collagen content (at days 21 and 28) and mRNA expression for collagen, tenomodulin and scleraxis.
  
  
  CONCLUSIONS
  IGF-I supplementation promotes early onset of tensile load induced collagen formation and tendon structural arrangement, whereas the FBS concentration routinely used in cultures diminishes collagen expression, collagen content and fibril formation.
authors.affiliation: Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Bispebjerg Bakke 23, Building 8, 2nd floor, 2400 Copenhagen, Denmark; Centre for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: andreashe@sund.ku.dk.
authors.forename: Andreas
authors.initials: A
authors.lastname: Herchenhan
authors.affiliation: Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Bispebjerg Bakke 23, Building 8, 2nd floor, 2400 Copenhagen, Denmark; Centre for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Monika L
authors.initials: ML
authors.lastname: Bayer
authors.affiliation: Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Bispebjerg Bakke 23, Building 8, 2nd floor, 2400 Copenhagen, Denmark; Centre for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Eliasson
authors.affiliation: Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Bispebjerg Bakke 23, Building 8, 2nd floor, 2400 Copenhagen, Denmark; Centre for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: S Peter
authors.initials: SP
authors.lastname: Magnusson
authors.affiliation: Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Bispebjerg Bakke 23, Building 8, 2nd floor, 2400 Copenhagen, Denmark; Centre for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Kjaer
mesh_terms: D000293:Adolescent; D000328:Adult; D003094:Collagen / Q000096:biosynthesis / Q000187:drug effects* / Q000648:ultrastructure; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013710:Tendons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D023822:Tissue Engineering; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003094:Collagen
keywords: 3D cell culture; Collagen content; Fetal bovine serum; Fibrillogenesis; Scleraxis; Tendon formation; Tenomodulin