The North West Embryonic Stem Cell Centre

Targeted differentiation to chondrocytes

Articular cartilage is a specialised connective tissue formed at the surface ends of long bones to dissipate biomechanical loads on the subchondral bone. The functional capacity of articular cartilage is reliant upon the maintenance and integrity of the extracellular matrix and the arrangement of its molecular components around its only cell type, the chondrocyte. As an avascular tissue, articular cartilage has a low capacity for self-repair following injury and trauma and is highly susceptible to degenerative diseases. Articular cartilage is a major therapeutic target for tissue engineering strategies as it is the root of debilitating conditions, such as osteoarthritis.

Pluripotent human embryonic stem cells (hESCs) have the potential to differentiate into every cell type of the body. However, the efficiency of spontaneous differentiation to some cell types, including chondrocytes, is poor. An important goal of NWESCC is to develop strategies of targeted differentiation which will bias a larger proportion of hESCs towards chondrocytes. Currently, hESCs are being cultured on 2D matrix substrates with the application of defined growth factors under serum-free conditions. This pushes the cells towards a mesodermal population and then onto chondroprogenitors which can ultimately be placed into pro-chondrogenic 3D cell aggregates for the formation of cartilage tissue.

Principal investigators

Collaborator

Senior research associate

A major therapeutic target

Control - PDGFRb
The aim of this project is to formulate a differentiation strategy where pluripotent hES cells are induced to form chondro-progenitor cells to produce cartilage.