Fachbereich Veterinärmedizin



    Mesenchymal Stem Cell-dependent Formation of Heterotopic Tendon-bone Insertions (Osteotendinous Junctions) (2010)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Shahab-Osterloh, Sandra
    Witte, Frank
    Hoffmann, Andrea
    Winkel, Andreas
    Laggies, Sandra
    Neumann, Berit
    Seiffart, Virginia
    Lindenmaier, Werner
    Gruber, Achim D
    Ringe, Jochen
    Häupl, Thomas
    Thorey, Fritz
    Willbold, Elmar
    Corbeau, Pierre
    Gross, Gerhard
    Stem cells; 28(9) — S. 1590–1601
    ISSN: 0250-6793
    DOI: 10.1002/stem.487
    Pubmed: 20882636
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
    +49 30 838 62450

    Abstract / Zusammenfassung

    Ligament-to-bone and tendon-to-bone interfaces (entheses, osteotendinous junctions [OTJs]) serve to dissipate stress between soft tissue and bone. Surgical reconstruction of these interfaces is an issue of considerable importance as they are prone to injury and the integration of bone and tendon/ligament is in general not satisfactory. We report here the stem cell-dependent spontaneous formation of fibrocartilaginous and fibrous entheses in heterotopic locations of the mouse if progenitors possess a tenogenic and osteo-/chondrogenic capacity. This study followed the hypothesis that enhanced Bone Morphogenetic Protein (BMP)-signaling in adult mesenchymal stem cells that are induced for tendon formation may overcome the tendon-inherent interference with bone formation and may thus allow the stem cell-dependent formation of tendon-bone interfaces. The tenogenic and osteo-/chondrogenic competence was mediated by the adeno- and/or lentiviral expression of the biologically active Smad8 signaling mediator (Smad8ca) and of Bone Morphogenetic Protein 2 (BMP2). Modified mesenchymal progenitors were implanted in subcutaneous or intramuscular sites of the mouse. The stem cell-dependent enthesis formation was characterized histologically by immunohistological approaches and by in situ hybridization. Transplantation of modified murine stem cells resulted in the formation of tendinous and osseous structures exhibiting fibrocartilage-type OTJs, while, in contrast, the viral modification of primary human bone marrow-derived mesenchymal stromal/stem cells showed evidence of fibrous tendon-bone interface formation. Moreover, it could be demonstrated that Smad8ca expression alone was sufficient for the formation of tendon/ligament-like structures. These findings may contribute to the establishment of stem cell-dependent regenerative therapies involving tendon/ligaments and to the improvement of the insertion of tendon grafts at bony attachment sites, eventually.