Open AccessTGF ‐β gene transfer and overexpression via rAAV vectors stimulates chondrogenic events in human bone marrow aspirates
Author(s) -
Frisch Janina,
ReyRico Ana,
Venkatesan Jagadeesh Kumar,
Schmitt Gertrud,
Madry Henning,
Cucchiarini Magali
Publication year - 2016
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.12774
Subject(s) - chondrogenesis , genetic enhancement , bone marrow , cartilage , articular cartilage repair , transforming growth factor , transforming growth factor beta , in vivo , adeno associated virus , biology , microbiology and biotechnology , in vitro , cancer research , recombinant dna , immunology , vector (molecular biology) , gene , medicine , pathology , articular cartilage , anatomy , osteoarthritis , genetics , alternative medicine
Abstract Genetic modification of marrow concentrates may provide convenient approaches to enhance the chondrogenic differentiation processes and improve the repair capacities in sites of cartilage defects following administration in the lesions. Here, we provided clinically adapted recombinant adeno‐associated virus ( rAAV ) vectors to human bone marrow aspirates to promote the expression of the potent transforming growth factor beta ( TGF ‐β) as a means to regulate the biological and chondrogenic activities in the samples in vitro . Successful TGF ‐β gene transfer and expression via rAAV was reached relative to control ( lacZ ) treatment (from 511.1 to 16.1 pg rh TGF ‐β/mg total proteins after 21 days), allowing to durably enhance the levels of cell proliferation, matrix synthesis, and chondrogenic differentiation. Strikingly, in the conditions applied here, application of the candidate TGF ‐β vector was also capable of reducing the hypertrophic and osteogenic differentiation processes in the aspirates, showing the potential benefits of using this particular vector to directly modify marrow concentrates to generate single‐step, effective approaches that aim at improving articular cartilage repair in vivo .