PhD defence Y.M.F. (Yannick) Nossin

Below is a brief summary of the dissertation:

Communication in any relationship is key. This also holds true for cells. Cells can communicate and interact in different ways with cells in their environment, including direct neighbors but also further removed ones. Cartilage is an interesting tissue in that regard, as its cell density could be best compared to the population density of Greenland, few and far apart. The majority of cartilage consists of an extracellular matrix which can be compared to scaffolding, providing stability, rigidity and elasticity to the tissue. The relatively simple makeup of cartilage meant that this tissue was expected to be the first replicated via tissue engineering. One approach to tissue engineering cartilage is to isolate cells and stimulate them to create cartilage extracellular matrix in culture. A common cell source is the bone marrow stroma. Bone marrow derived mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs), can be differentiated into chondrocytes with a cocktail of factors. However, these cells don’t know when to stop, and they continue their maturation from cartilage towards bone formation in a process called endochondral ossification. In contrast, using chondrocytes - the cells residing in cartilage - to tissue engineer cartilage, leads to a stable cartilage construct. To understand why chondrocytes make stable cartilage whereas MSCs form transient cartilage that is prone to ossification, we investigated their communication. To get a glimpse into the messages sent by different cells, I collected the factors they release (the releasate) in the medium that was used to keep them alive (conditioned medium). In this thesis I was able to show that cartilage and our tissue engineered substitute are not only quite communicative but also what they can achieve with this communication. One major communication partner that I took a closer look at in this thesis were endothelial cells, which make up blood vessels. The process of these blood vessels growing is called angiogenesis, which is interesting as it plays a major role during endochondral ossification (the transition from cartilage to bone). This process of endochondral ossification can be observed in the growth plate and is the mechanism that drives the growth of all our long bones but can also be observed during osteoarthritis where articular cartilage degenerates. To better understand this process, the central question I wanted to answer in this thesis was: What is the impact of cartilage releasate on angiogenesis during endochondral ossification?