Published in

Wiley Open Access, Journal of Cellular and Molecular Medicine, 3(20), p. 430-440, 2016

DOI: 10.1111/jcmm.12774

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TGF‐β gene transfer and overexpression viarAAV vectors stimulates chondrogenic events in human bone marrow aspirates

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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-beta) as a means to regulate the biological and chondrogenic activities in the samples in vitro. Successful TGF-beta gene transfer and expression via rAAV was reached relative to control (lacZ) treatment (from 511.1 to 16.1 pg rhTGF-beta/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-beta 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.