Background: Application of genetically modified bone marrow concentrates in articular cartilage lesions is a\npromising approach to enhance cartilage repair by stimulating the chondrogenic differentiation processes in sites\nof injury.\nMethod: In the present study, we examined the potential benefits of transferring the proliferative and\npro-chondrogenic basic fibroblast growth factor (FGF-2) to human bone marrow aspirates in vitro using the\nclinically adapted recombinant adeno-associated virus (rAAV) vectors to monitor the biological and chondrogenic\nresponses over time to the treatment compared with control (lacZ) gene application.\nResults: Effective, significant FGF-2 gene transfer and expression via rAAV was established in the aspirates relative\nto the lacZ condition (from ~ 97 to 36 pg rhFGF-2/mg total proteins over an extended period of 21 days).\nAdministration of the candidate FGF-2 vector led to prolonged increases in cell proliferation, matrix synthesis, and\nchondrogenesis but also to hypertrophic and terminal differentiation in the aspirates.\nConclusion: The present evaluation shows the advantages of rAAV-mediated FGF-2 gene transfer to conveniently\nmodify bone marrow concentrates as a future approach to directly treat articular cartilage lesions, provided that\nexpression of the growth factor is tightly regulated to prevent premature hypertrophy in vivo.
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