Microenviromental influence of cartilage and bone explants on chrondrogenic differentation of multipotent mesenchymal stem cells

Ex vivo production of tissue-engineered functional cartilage with articular characteristics remains a challenge, in vivo regeneration of chondral and osteochondral defects remains still a vision. To effectively address the problems a better understanding of microenvironmental cues and the modulating influence of neighbouring cells and tissue interfaces on chondrogenic differentiation of chondroprogenitor cells are essential. We intend to compare impact of cartilage / subchondral bone surfaces on chondrogenic differentiation of mesenchymal stem cells (MSCs) and properties of regenerated tissue. Furthermore, we will test whether direct cell-to-cell contact between differentiated chondrocytes and undifferentiated MSCs in these experimental set ups will enhance differentiation and improve hyaline cartilage like quality and biomechanical properties of regenerated tissue. This study is designed to identify microenvironmental conditions which promote, prevent or interfere with chondrogenic differentiation of MSCs and to analyse their impact on molecular properties and quality of regenerated tissue. For MSC based cartilage repair, inhibition of hypertrophy and the endochondral ossification pathway in addition to stabilization of the hyaline cartilaginous phenotype of the regenerated tissue is a prerequisite for successful articular cartilage tissue regeneration.