Photo: University of Basel, Christian Flierl
Cartilage cells from the nasal septum can not only help repair damaged cartilage in the knee. They can also withstand the chronic inflammatory tissue environment in osteoarthritis and even counteract the inflammation, as researchers from the University of Basel and the University Hospital Basel report.
A research team at the Department of Biomedicine at the University of Basel and the University Hospital Basel is growing cartilage tissue from cells in the nasal septum to repair articular cartilage in the knee. They have already succeeded in doing this in the context of initial clinical studies with isolated cartilage damage. Now the team around Prof. Dr. Ivan Martin and Prof. Dr. Andrea Barbero that the approach could also be suitable for degenerative joint diseases such as osteoarthritis. Their results have been published in the journal Science Translational Medicine.
Osteoarthritis is characterized by the breakdown of cartilage, which can lead to severe pain when moving. Previous therapy has consisted of treating the inflammation and pain until a prosthetic knee joint becomes inevitable. However, joint prostheses have a limited shelf life, which makes multiple operations necessary, especially in younger patients.
A possible alternative could be the repair of the articular cartilage with the help of cultured cartilage tissue. To do this, the research team, in collaboration with orthopedic and plastic surgeons from the University Hospital Basel, takes a tissue sample from the patient's nasal septum, cultivates the cartilage cells it contains and uses them to grow a layer of cartilage, which is then surgically inserted into the knee joint.
In contrast to sports injuries, for example, the tissue surrounding the knee in osteoarthritis is characterized by persistent inflammatory reactions. “We first had to test whether the cartilage replacement was attacked and degenerated by the inflammatory factors,” explains Ivan Martin.
The researchers led by Prof. Martin's doctoral student Lina Acevedo Rua, the project leader Dr. Karoliina Pelttari and the orthopedic surgeon PD Dr. Marcus Mumme first tested the cultured human cartilage tissue in the presence of inflammatory factors. To do this, they used various cell culture models in the laboratory and small test animals. They then tested the durability of the cartilage tissue, even with simultaneous inflammatory and mechanical stress. To do this, they used cartilage cells from the nose of sheep in the arthritic knee joint of the same animals.
The results of the animal experiments were promising: not only did the tissue from nasal cartilage cells prove to be very robust, it also seemed to counteract the inflammatory reactions. Further analyzes showed that this effect is mainly due to the fact that a molecular signal path that is chronically over-activated in osteoarthritis (the so-called WNT signal path) was slowed down by the presence of the nasal cartilage cells.
Prof. Martin explains the astonishing properties of the nasal cartilage as follows: “Unlike the cartilage tissue of the joints, these cartilage cells come from precursor cells from a specialized embryonic tissue, the neuroectoderm, and are therefore characterized by a high ability to regenerate and adapt. Tissue grown from nasal cartilage cells could also have these special properties. "After the successful experiments on animals, the researchers also tested the approach on two young patients who suffered from severe osteoarthritis due to a misalignment of the leg bones. Otherwise, the next step in her treatment would have been a knee joint prosthesis.
After inserting the replacement cartilage, which the researchers had grown from the patient's own nasal cartilage cells, the two test subjects reported a reduction in pain and an increased quality of life. In one of the two patients, the researchers were also able to use MRI images to determine that the bones in the knee joint were again a greater distance apart than before - an indication of the joint's recovery. With the second patient, due to the travel restrictions during the pandemic, they were unable to take MRI images and could only ask him about his subjective impressions.
Since the misalignment of the bones in both patients was corrected surgically and the most likely cause of their osteoarthritis could be eliminated, the researchers are confident that they will be able to manage without a knee joint prosthesis for a long time to come.
"With our results, we have laid the biological basis for a therapy and are cautiously optimistic," says Martin. Now the approach to the treatment of patellofemoral osteoarthritis has to be proven in in-depth clinical studies, for which the team receives financial support as part of an innovation focus from the University Hospital Basel. In addition, the researchers want to further develop the method for other types of osteoarthritis in the future in order to be able to treat a wider range of patients.