Functional Cartilage Tissue Engineering with Adult Stem Cells: Current Status and Future Directions

Abstract

Adult mesenchymal stem cells (MSCs) hold great promise for engineering replacements for damaged or degraded articular cartilage. This promise has long been contemplated, and its arrival has recently been marked by the implantation of engineered human trachea using autologous adult stem cells [1]. While tracheal cartilage is not the same as the articulating cartilage lining the ends of load bearing joints, the demonstration of in vivo efficacy provides a major step forward clinically. However, not all progress with MSC-based cartilage has been successful and considerable challenges remain in the realization of these constructs for load-bearing applications. Thus the intent of this chapter is to define the functional metrics required for engineering articular cartilage, and to situate the current state of MSC-based constructs within this framework. In doing so, we briefly define the components and function of the native tissue, and review the progress made to date using differentiated cartilage cells (chondrocytes) for cartilage tissue engineering. This discussion includes methods of formation, biochemical formulations for enhancing in vitro development, as well as progress made towards using mechanical forces to further direct maturation. We next overview the origins and applications of adult multi-potential stem cells, and discuss how routes towards cartilage tissue engineering with stem cells match (or fail to match) those approaches that were successful using differentiated cells. In particular, we describe new requirements for cartilage formation with MSCs, and outline several research areas that may inform this new direction in cartilage tissue engineering.