Co-delivery of TGF-β3 and COL I-targeting shRNA with adenoviral and lentiviral vectors for COL I-surpressed in vitro chondrogenesis

• Main Author: M. K. Mohamed Idris
• Other Authors: Wang Dongan
• Format: Final Year Project
• Language: English
• Published: 2011
• Subjects: DRNTU::Science::Biological sciences::Microbiology::Virology; DRNTU::Science::Medicine::Tissue engineering
• Online Access: http://hdl.handle.net/10356/45690
• Institution: Nanyang Technological University

Cartilage degeneration poses a challenge to clinicians in spite of the various therapies that have been developed for its treatment. Cell-based therapy is promising due to its ability to restore the structure and function of the native cartilage as much as possible. Stromal-derived mesenchymal stem cells (SMSCs) can be cultured to undergo chondrogenesis in-vitro. However, a serious drawback in this process is that the cells become hypertrophic and undergo apoptosis. We propose dosing the SMSCs with TGF-β3 to promote chondrogenesis. Simultaneously, since type I collagen (Col I) is inevitably elevated along the passages, it will undermine the mechanical strength of engineered cartilage. RNA interference (RNAi) would therefore be utilized to reduce its expression. To deliver both TGF-β3 and Col I-targeted small hairpin RNA (shRNA) to the cells, a variety of viral vectors would be tested, including adenoviral vectors and lentiviral vectors. Adenoviral vector induces a transient expression due to its episomal performance, whereas lentiviral vector leads to a more sustained expression since the vector can integrate its genome together with transgenes into the host genome. The results of this research suggest the promising potential of these viral vectors for the engineering of articular cartilage.