PhD defence J. (Johannes) Lehmann

Brief summary:

When cartilage is lost in joints and spine, the bones collide and every move becomes excruciatingly painful; damage to the airway cartilage risks suffocation while the destruction of ear and nose cartilage can disfigure the face. Mesenchymal stem cells from the bone marrow can be stimulated to generate new cartilage, however they lose that ability in cell culture. We found that mesenchymal stem cells lose their ability to multiply and from cartilage due to senescence, a cellular stress response associated with ageing. Unlike in human ageing, where senescence takes decades to be noticeable, we found that in cell cultures senescence spreads through the cell population within days. Activating WNT signalling stopped senescence from spreading by blocking the production of the senescence-transmitting signalling molecules. Targeting the spread of senescence may thus open up new possibilities to engineer tissues using stem cells from elderly patients. 
We can help cells regenerate cartilage by placing them into the extracellular matrix of cartilage. This complex, cross-linked fibre network is difficult to reproduce synthetically, but we can remove cells from donor tissue and retain the extracellular matrix. These decellularized scaffolds can then be refilled with cells from the patient to allow the tissue to function again. However, the lack of blood vessels in cartilage makes it difficult to get cells out and impossible to get cells in. We now show that removing elastin fibres from ear cartilage using enzymes generates channels that allow recellularization for cartilage defect repair.