title: Stem cells and basic fibroblast growth factor failed to improve tendon healing: an in vivo study using lentiviral gene transfer in a rat model.
abstract: BACKGROUND
  The aim of this controlled study was to investigate the influence of mesenchymal stem cells (MSCs) and lentiviral (LV) expression of basic fibroblast growth factor (bFGF) on tendon remodeling in an in vivo rat model of an Achilles tendon defect.
  
  
  METHODS
  In eighty-four male Lewis rats, complete 2.4-mm tendon defects were created and were either left untreated (the phosphate-buffered saline solution [PBS] group) or were treated with mesenchymal stem cells expressing enhanced green fluorescent protein (the MSC-LV-eGFP group) or with mesenchymal stem cells expressing basic fibroblast growth factor lentivirally (the MSC-LV-bFGF group). After fourteen and twenty-eight days, the tendons were harvested and analyzed biomechanically and immunohistologically.
  
  
  RESULTS
  After fourteen days, both mesenchymal stem cell groups were slightly superior in biomechanical testing. However, only the PBS control group showed a significant increase in biomechanical results over time (fourteen versus twenty-eight days; p = 0.012). Biomechanical results were better after twenty-eight days for the control group than for both MSC groups. However, the difference was significant only with regard to the stiffness results in the comparison of the PBS control and the eGFP stem cell group (p = 0.024). Histologically, the MSC groups had no better results than the control group after fourteen and twenty-eight days. In immunohistology, only labeling for type-I procollagen was strongly increased in both MSC groups in comparison with the PBS control group (p = 0.0009 for the MSC-LV-bFGF group and p = 0.0041 for the MSC-LV-eGFP group at fourteen days, and p = 0.004 and p = 0.132, respectively, at twenty-eight days). There were no significant differences in the immunohistological results between the stem cell groups.
  
  
  CONCLUSIONS
  The biomechanical and immunohistological results showed that mesenchymal stem cells in both groups had only partially positive effects on tendon remodeling in the initial stages; however, in later stages, stem cells had potentially negative effects on biomechanical results. The additional expression of bFGF in stem cells had negligible effects on tendon remodeling.
  
  
  CONCLUSIONS
  Preliminary studies using stem cells are partially promising; however, there are no relevant clinical data showing that stem cells are of significant benefit. The present study should lead to a more critical evaluation and thoughtful use of stem cells in humans until more clinical data are available.
authors.affiliation: BG Trauma Clinic Tübingen, University Hospital Tübingen, Schnarrenbergstr. 95, 72076 Tübingen, Germany. E-mail address for T.M. Kraus: tkraus@bgu-tuebingen.de.
authors.forename: T M
authors.initials: TM
authors.lastname: Kraus
authors.affiliation: Departments of Sports Orthopaedics (G.W., L.L., S.B., A.B.I., and S.V.) and Traumatology (F.B.I.), and the Institute of Experimental Oncology and Therapy Research (A.W., D.H., and M.A.), Klinikum rechts der Isar der Technischen Universität München, Ismani.
authors.forename: F B
authors.initials: FB
authors.lastname: Imhoff
authors.affiliation: Departments of Sports Orthopaedics (G.W., L.L., S.B., A.B.I., and S.V.) and Traumatology (F.B.I.), and the Institute of Experimental Oncology and Therapy Research (A.W., D.H., and M.A.), Klinikum rechts der Isar der Technischen Universität München, Ismani.
authors.forename: G
authors.initials: G
authors.lastname: Wexel
authors.affiliation: Departments of Sports Orthopaedics (G.W., L.L., S.B., A.B.I., and S.V.) and Traumatology (F.B.I.), and the Institute of Experimental Oncology and Therapy Research (A.W., D.H., and M.A.), Klinikum rechts der Isar der Technischen Universität München, Ismani.
authors.forename: A
authors.initials: A
authors.lastname: Wolf
authors.affiliation: Departments of Sports Orthopaedics (G.W., L.L., S.B., A.B.I., and S.V.) and Traumatology (F.B.I.), and the Institute of Experimental Oncology and Therapy Research (A.W., D.H., and M.A.), Klinikum rechts der Isar der Technischen Universität München, Ismani.
authors.forename: D
authors.initials: D
authors.lastname: Hirsch
authors.affiliation: Departments of Sports Orthopaedics (G.W., L.L., S.B., A.B.I., and S.V.) and Traumatology (F.B.I.), and the Institute of Experimental Oncology and Therapy Research (A.W., D.H., and M.A.), Klinikum rechts der Isar der Technischen Universität München, Ismani.
authors.forename: L
authors.initials: L
authors.lastname: Lenz
authors.affiliation: BG Trauma Clinic Tübingen, University Hospital Tübingen, Schnarrenbergstr. 95, 72076 Tübingen, Germany. E-mail address for T.M. Kraus: tkraus@bgu-tuebingen.de.
authors.forename: U
authors.initials: U
authors.lastname: Stöckle
authors.affiliation: Departments of Sports Orthopaedics (G.W., L.L., S.B., A.B.I., and S.V.) and Traumatology (F.B.I.), and the Institute of Experimental Oncology and Therapy Research (A.W., D.H., and M.A.), Klinikum rechts der Isar der Technischen Universität München, Ismani.
authors.forename: S
authors.initials: S
authors.lastname: Buchmann
authors.affiliation: Department of Orthopaedic Surgery, University of Rostock, Doberaner Str. 142, 18057 Rostock, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Tischer
authors.affiliation: Departments of Sports Orthopaedics (G.W., L.L., S.B., A.B.I., and S.V.) and Traumatology (F.B.I.), and the Institute of Experimental Oncology and Therapy Research (A.W., D.H., and M.A.), Klinikum rechts der Isar der Technischen Universität München, Ismani.
authors.forename: A B
authors.initials: AB
authors.lastname: Imhoff
authors.affiliation: Anatomische Anstalt, Ludwig Maximilians Universität, Pettenkoferstr. 11, D-80336 Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Milz
authors.affiliation: Departments of Sports Orthopaedics (G.W., L.L., S.B., A.B.I., and S.V.) and Traumatology (F.B.I.), and the Institute of Experimental Oncology and Therapy Research (A.W., D.H., and M.A.), Klinikum rechts der Isar der Technischen Universität München, Ismani.
authors.forename: M
authors.initials: M
authors.lastname: Anton
authors.affiliation: Departments of Sports Orthopaedics (G.W., L.L., S.B., A.B.I., and S.V.) and Traumatology (F.B.I.), and the Institute of Experimental Oncology and Therapy Research (A.W., D.H., and M.A.), Klinikum rechts der Isar der Technischen Universität München, Ismani.
authors.forename: S
authors.initials: S
authors.lastname: Vogt
mesh_terms: D000125:Achilles Tendon / Q000293:injuries* / Q000502:physiology; D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006614:Hindlimb; D007150:Immunohistochemistry; D016086:Lentivirus; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D014161:Transduction, Genetic / Q000379:methods; D014759:Viral Envelope Proteins / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects*
chemical_list: C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C485184:enhanced green fluorescent protein; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins