Reconstruct large osteochondral defects of the knee with hIGF-1 gene enhanced Mosaicplasty

Overexpression of human IGF-I via direct rAAV-mediated gene transfer improves the early repair of articular cartilage defects in vivo

“…Here, for the first time to our best knowledge, we investigated the ability of rAAV-mediated IGF-I overexpression to enhance the repair of osteochondral defects in rabbit knee joints early on following direct, local gene transfer in light of reports showing partial effects of a recombinant growth factor [19][20][21][22] or of IGF-I gene transfer using less efficient non-viral and adenoviral vectors in complex indirect strategies, [23][24][25][26] and based on our own findings that the present rAAV IGF-I vector can significantly remodel human osteoarthritic cartilage. 30 The data indicate that sustained transgene expression can be achieved in rabbit MSCs and chondrocytes in vitro over time (up to 21 days) at high efficiencies (up to 82%), consistent with previous reports in these cell types 14 or when applying the present IGF-I vector to human chondrocytes.…”

“…36,42,46 For comparison, improved cartilage repair was also reported in similar models when providing IGF-I as a recombinant molecule with short half-life, [19][20][21][22] although very high doses of the factor were needed to achieve therapeutic effects (25 μg in horses, 200 ng in rabbits). On the other side, expression of IGF-I via implantation of non-virally [24][25][26] or adenovirally modified cells 23 (chondrocytes, MSCs) in a biomaterial also promoted cartilage repair in vivo. In contrast to such a complex approach, the current strategy based on highly efficient and safe rAAV vectors may provide convenient (one-step) options to treat cartilage lesions, showing again the strong value of this class of vector for clinically relevant gene transfer protocols.…”

“…[19][20][21][22] Application of cells (chondrocytes, mesenchymal stem cells (MSCs)) modified to overexpress IGF-I via non-viral or adenoviral vector gene transfer has also been reported in cartilage defects using different types of scaffolds. [23][24][25][26] In addition to the complexity of such an indirect approach, the use of non-viral and adenoviral vectors is still restricted by their low efficacy and/or immunogenicity. Instead, vectors derived from the human nonpathogenic, replication-defective adeno-associated virus (AAV) have promising features for in vivo therapy as recombinant AAV (rAAV) vectors do not carry viral coding sequences, making them less immunogenic.…”

Gene therapy for chondral and osteochondral regeneration: is the future now?

“…Chemical methods, employed in preclinical studies, form complexes with DNA and various macromolecules, including liposomes, cationic polysaccharide and non-liposomal lipid-based transfection [14][15][16][17][18][19][20][21]. They can deliver large genes and are easy to produce on a large scale.…”

“…The largest group includes GF genes, such as IGF-1 [8,[15][16][17][18]20 [63]. VEGF, transfected into MSCs, induces arthritic-like changes in the joints and the co-transfection with sFlt-1 ameliorated this condition in osteochondral defects [72].…”