Mesenchymal stem cell death in three-dimensional agarose culture for cartilage tissue engineering applications: Progression, factors, and prevention

Engineered cartilage based on adult derived mesenchymal stem cells (MSCs) would be an ideal treatment for cartilage damage and osteoarthritis. However, insufficient mechanical properties in constructs formed using this cell source limits in vivo application. Here we identify a rapid and then progressive decline in MSC viability in 3D agarose tissue engineered constructs. We show that this decline in viability is linked to metabolic activity and waste production by these cells, and that they are poorly equipped to handle this demanding environment compared to cells derived from the native tissue. Blockade of early cell death may be controlled through small molecule inhibitors of apoptosis.