Interaction between cartilage / subchondral interfaces and MSC in vitro and in vivo

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Ex vivo production of tissue-engineered functional cartilage with articular characteristics remains still to be optimized and in vivo regeneration of chondral defects is a real challenge. 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. In this study, we are analysing the impact of cartilage/subchondral bone surfaces on chondrogenic differentiation of mesenchymal stem cells (MSC) and properties of regenerated tissue. We have detected that contact to osteoarthritic articular cartilage and subchondral bone surfaces represses gene expression and biosynthesis of structural molecules in differentiated chondrocytes and undifferentiated MSC. Adaptation of the human in vitro coculture systems to the ovine system will allow a comparison of the response of pathological OA-tissues with the response of healthy tissues. Subsequently, we will integrate cell-based implants into focal full-thickness chondral defects in a large animal sheep model using 1) chondrogenically pre-differentiated autologous MSC and 2) a mixed culture of MSC with autologous chondrocytes, both in fibrin gel constructs. This will allow us to test the influence of signals from differentiated cells in the microenvironment and to analyse the interaction between the chondral interface and the implanted cells in vivo. In this follow up project we pursue two main goals:1. We want to identify responsible repressive factor(s) derived from late OA-tissue/chondrocytes which modulate gene and protein expression 2. We want to analyse the interaction between healthy (or early OA) cartilage tissue and MSC in vivo