title: The initiation of embryonic-like collagen fibrillogenesis by adult human tendon fibroblasts when cultured under tension.
abstract: Tendon fibroblasts synthesize collagen and form fibrils during embryonic development, but to what extent mature fibroblasts are able to recapitulate embryonic development and develop normal tendon structure is unknown. The present study examined the capability of mature human tendon fibroblasts to initiate collagen fibrillogenesis when cultured in fixed-length fibrin gels. Fibroblasts were dissected from semitendinosus and gracilis tendons from healthy humans and cultured in 3D linear fibrin gels. The fibroblasts synthesized an extracellular matrix of parallel collagen fibrils that were aligned along the axis of tension. The fibrils had a homogeneous narrow diameter that was similar to collagen fibrils occurring in embryonic tendon. Immunostaining showed colocalization of collagen type I with collagen III, XII and XIV. A fibronectin network was formed in parallel with the collagen, and fibroblasts stained positive for integrin alpha(5). Finally, the presence of cell extensions into the extracellular space with membrane-enclosed fibrils in fibripositors indicated characteristics of embryonic tendon. We conclude that mature human tendon fibroblasts retain an intrinsic capability to perform collagen fibrillogenesis similar to that of developing tendon, which implies that the hormonal/mechanical milieu, rather than intrinsic cellular function, inhibits regenerative potential in mature tendon.
authors.affiliation: Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital, and Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, 2400 Copenhagen, Denmark. mlbayer82@gmail.com
authors.forename: Monika L
authors.initials: ML
authors.lastname: Bayer
authors.forename: Chin-Yan C
authors.initials: CY
authors.lastname: Yeung
authors.forename: Karl E
authors.initials: KE
authors.lastname: Kadler
authors.forename: Klaus
authors.initials: K
authors.lastname: Qvortrup
authors.forename: Keith
authors.initials: K
authors.lastname: Baar
authors.forename: René B
authors.initials: RB
authors.lastname: Svensson
authors.forename: S Peter
authors.initials: SP
authors.lastname: Magnusson
authors.forename: Michael
authors.initials: M
authors.lastname: Krogsgaard
authors.forename: Manuel
authors.initials: M
authors.lastname: Koch
authors.forename: Michael
authors.initials: M
authors.lastname: Kjaer
mesh_terms: D000328:Adult; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism; D005337:Fibrin / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D005782:Gels / Q000737:chemistry; D006801:Humans; D013710:Tendons / Q000166:cytology*; D013718:Tensile Strength; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D005782:Gels; D005337:Fibrin; D003094:Collagen