Open AccessPeripheral blood aspirates overexpressing IGF‐I via rAAV gene transfer undergo enhanced chondrogenic differentiation processes
Author(s) -
Frisch Janina,
Orth Patrick,
ReyRico Ana,
Venkatesan Jagadeesh Kumar,
Schmitt Gertrud,
Madry Henning,
Kohn Dieter,
Cucchiarini Magali
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13190
Subject(s) - sox9 , chondrogenesis , cartilage , transduction (biophysics) , anabolism , genetic enhancement , articular cartilage repair , reporter gene , in vivo , growth factor , microbiology and biotechnology , medicine , cancer research , pathology , biology , gene expression , gene , endocrinology , anatomy , articular cartilage , receptor , osteoarthritis , genetics , biochemistry , alternative medicine
Implantation of peripheral blood aspirates induced towards chondrogenic differentiation upon genetic modification in sites of articular cartilage injury may represent a powerful strategy to enhance cartilage repair. Such a single‐step approach may be less invasive than procedures based on the use of isolated or concentrated MSCs, simplifying translational protocols in patients. In this study, we provide evidence showing the feasibility of overexpressing the mitogenic and pro‐anabolic insulin‐like growth factor I (IGF‐I) in human peripheral blood aspirates via rAAV‐mediated gene transfer, leading to enhanced proliferative and chondrogenic differentiation (proteoglycans, type‐II collagen, SOX9) activities in the samples relative to control (reporter rAAV‐ lacZ ) treatment over extended periods of time (at least 21 days, the longest time‐point evaluated). Interestingly, IGF‐I gene transfer also triggered hypertrophic, osteo‐ and adipogenic differentiation processes in the aspirates, suggesting that careful regulation of IGF‐I expression may be necessary to contain these events in vivo . Still, the current results demonstrate the potential of targeting human peripheral blood aspirates via therapeutic rAAV transduction as a novel, convenient tool to treat articular cartilage injuries.