ENHANCING MESENCHYMAL STEM CELL

Articular cartilage provides a bearing surface for transmitting forces across joints. The poor ability of cartilage to self-repair has motivated efforts to engineer replacement tissues, and mesenchymal stem cells (MSCs), which can undergo chondrogenesis, have emerged as a promising cell source. To date however, the functional properties of MSC-based constructs remain lower than those of the native tissue and of chondrocyte-based constructs cultured identically. Therefore, the overall objective of this thesis is to better understand the transcriptional and functional limitations underlying chondrogenic differentiation and enhance MSC chondrogenesis. Toward this end, established tissue engineering strategies from the chondrocyte literature were applied. Specifically, the effects of cell seeding density, media formulation and mechanical stimulation were examined with respect to functional growth. Transient application of TGF-β3 improved the compressive properties of MSC-laden constructs, but only when constructs were formed at a higher seeding density. Long-term dynamic compression initiated 3 days after MSC encapsulation impaired functional properties; in contrast, dynamic compression initiated after 3 weeks of chondrogenic pre-culture improved mechanical function. While these strategies enhanced functional chondrogenesis, the compressive properties achieved were ~50