title: Stem cells and bFGF in tendon healing: Effects of lentiviral gene transfer and long-term follow-up in a rat Achilles tendon defect model.
abstract: BACKGROUND
  The influence of stem cells and lentiviral expression of basic fibroblastic growth factor (bFGF) on tendon healing and remodelling was investigated in an in-vivo long-term (12 weeks) rat Achilles tendon defect model.
  
  
  METHODS
  In sixty male Lewis rats, complete tendon defects (2.4 mm) were created and either left untreated (PBS) or treated by injection of stem cells lentivirally expressing the enhanced green fluorescence marker gene eGFP (MSC-LV-eGFP) or basic fibroblast growth factor bFGF (MSC-LV-bFGF). Tendons were harvested after 12 weeks and underwent biomechanical and (immuno)-histological analysis.
  
  
  RESULTS
  After 12 weeks the mean ultimate load to failure ratio (treated side to contralateral side) in biomechanical testing reached 97 % in the bFGF-group, 103 % in the eGFP-group and 112 % in the PBS-group. Also in the stiffness testing both MSC groups did not reach the results of the PBS group. Histologically, the MSC groups did not show better results than the control group. There were clusters of ossifications found in all groups. In immunohistology, only the staining collagen-type-I was strongly increased in both MSC groups in comparison to PBS control group. However, there were no significant differences in the (immuno)-histological results between both stem cell groups.
  
  
  CONCLUSIONS
  The biomechanical and (immuno)-histological results did not show positive effects of the MSC groups on tendon remodelling in a long-term follow-up. Interestingly, in later stages stem cells had hardly any effects on biomechanical results. This study inspires a critical and reflected use of stem cells in tendon healing.
authors.affiliation: Department for Sports Orthopaedics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. kraus.tobias@gmail.com.|BG Trauma Center, Eberhard Karls University Tübingen, Tübingen, Germany. kraus.tobias@gmail.com.
authors.forename: T M
authors.initials: TM
authors.lastname: Kraus
authors.affiliation: Department for Sports Orthopaedics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: F B
authors.initials: FB
authors.lastname: Imhoff
authors.affiliation: Department for Sports Orthopaedics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Reinert
authors.affiliation: Department for Sports Orthopaedics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Wexel
authors.affiliation: Institute of Molecular Immunology/Experimental Oncology and Therapy Research, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wolf
authors.affiliation: Institute of Molecular Immunology/Experimental Oncology and Therapy Research, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Hirsch
authors.affiliation: Department for Sports Orthopaedics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hofmann
authors.affiliation: BG Trauma Center, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Stöckle
authors.affiliation: Department for Sports Orthopaedics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Buchmann
authors.affiliation: Department of Orthopaedic Surgery, University of Rostock, Rostock, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Tischer
authors.affiliation: Department for Sports Orthopaedics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: A B
authors.initials: AB
authors.lastname: Imhoff
authors.affiliation: Anatomische Anstalt, Ludwig Maximillians Universität, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Milz
authors.affiliation: Institute of Molecular Immunology/Experimental Oncology and Therapy Research, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Anton
authors.affiliation: Department for Sports Orthopaedics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.|Department of Sports Orthopaedics, Hessing Stiftung, Augsburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Vogt
mesh_terms: D000125:Achilles Tendon / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D000818:Animals; D001696:Biomechanical Phenomena; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D011917:Rats, Inbred Lew; D020127:Recovery of Function; D013708:Tendon Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D014945:Wound Healing
chemical_list: D016222:Fibroblast Growth Factor 2
keywords: Growth factor; Lentiviral vector; Mesenchymal stem cells (MSCs); Tendon healing; bFGF