title: Effects of rAAV-mediated FGF-2 gene transfer and overexpression upon the chondrogenic differentiation processes in human bone marrow aspirates.
abstract: BACKGROUND
  Application of genetically modified bone marrow concentrates in articular cartilage lesions is a promising approach to enhance cartilage repair by stimulating the chondrogenic differentiation processes in sites of injury.
  
  
  METHODS
  In the present study, we examined the potential benefits of transferring the proliferative and pro-chondrogenic basic fibroblast growth factor (FGF-2) to human bone marrow aspirates in vitro using the clinically adapted recombinant adeno-associated virus (rAAV) vectors to monitor the biological and chondrogenic responses over time to the treatment compared with control (lacZ) gene application.
  
  
  RESULTS
  Effective, significant FGF-2 gene transfer and expression via rAAV was established in the aspirates relative to the lacZ condition (from ~ 97 to 36 pg rhFGF-2/mg total proteins over an extended period of 21 days). Administration of the candidate FGF-2 vector led to prolonged increases in cell proliferation, matrix synthesis, and chondrogenesis but also to hypertrophic and terminal differentiation in the aspirates.
  
  
  CONCLUSIONS
  The present evaluation shows the advantages of rAAV-mediated FGF-2 gene transfer to conveniently modify bone marrow concentrates as a future approach to directly treat articular cartilage lesions, provided that expression of the growth factor is tightly regulated to prevent premature hypertrophy in vivo.
authors.affiliation: Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr. Bldg 37, D-66421, Homburg/Saar, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Frisch
authors.affiliation: Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr. Bldg 37, D-66421, Homburg/Saar, Germany.
authors.forename: Jagadeesh K
authors.initials: JK
authors.lastname: Venkatesan
authors.affiliation: Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr. Bldg 37, D-66421, Homburg/Saar, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Rey-Rico
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg/Saar, Germany.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Zawada
authors.affiliation: Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr. Bldg 37, D-66421, Homburg/Saar, Germany.
authors.forename: Gertrud
authors.initials: G
authors.lastname: Schmitt
authors.affiliation: Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr. Bldg 37, D-66421, Homburg/Saar, Germany.|Department of Orthopaedic Surgery, Saarland University Medical Center, Homburg/Saar, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Madry
authors.affiliation: Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr. Bldg 37, D-66421, Homburg/Saar, Germany. mmcucchiarini@hotmail.com.
authors.forename: Magali
authors.initials: M
authors.lastname: Cucchiarini
keywords: Cartilage repair; FGF-2; Gene therapy; Human bone marrow aspirates; rAAV