Construction and application of adenoviral and lentiviral vectors to deliver transforming growth factor β3 and type I collagen-targeting SHRNA for engineered articular chondrogenesis.
Date of Issue2011
School of Chemical and Biomedical Engineering
In this dissertation, we aim to induce type I collagen (Col I)-suppressed chondrogenesis in synovium-derived mesenchymal stem cells (SMSCs) or chondrocytes within 3-dimensional (3D) alginate hydrogel system with the use of adenoviral and/or lentiviral vectors to deliver both transforming growth factor β3 (TGF-β3) and Col I-targeting short hairpin RNA (shRNA). A collection of single-functioning and dual-functioning adenoviral/lentiviral vectors that express TGF-β3 and/or Col I-targeting shRNA were constructed and tested in SMSCs and chondrocytes encapsulated in 3D alginate hydrogel for Col I-suppressed chondrogenesis. One dual-functioning lentiviral vector with particular transgene arrangement (LV-1 in Chapter 4), and the combination of TGF-β3-expressing lentiviral vector and shRNA-encoding adenoviral vector (LV-T+Ad-sh in Chapter 5) were found to be relatively more effective than others in inducing chondrogenesis in SMSCs. Besides, the above dual-functioning lentiviral vector was also effective in inducing chondrocyte redifferentiation in 3D alginate hydrogel. These results suggest the promising potential of these viral vectors for the engineering of articular cartilage.