Future treatments for knee osteoarthritis could come from cartilage harvested from the nose, according to Swiss researchers.
A series of experiments in animal models and in patients with knee OA by a University of Basel team has shown that nasal septum cartilage cell implants can help repair degenerative knee cartilage damage.
Working with orthopaedic surgeons, the team have shown that nasal chondrocyte–based tissue-engineered cartilage (N-TEC) can be transplanted into a knee with OA, withstand the chronic inflammatory tissue environment and even counteract the inflammation.
The team led by Professor Ivan Martin and Professor Andrea Barbero started with in vitro tests that showed nasal septum cartilage maintained cartilaginous properties when exposed in vitro to inflammatory stimuli found in osteoarthritic joints and favourably altered the inflammatory profile of cells from osteoarthritic joints.
These effects were at least partially mediated by down-regulation of the WNT (wingless/integrated) signalling pathway through sFRP1 (secreted frizzled-related protein-1), they wrote in Science Translational Medicine.
The team followed this by showing that nasal septum cartilage could survive and engraft in vivo, in animal models that reproduced a human osteochondral OA tissue environment, as well as in sheep articular cartilage defects that mimicked degenerative settings.
Subsequently they tested the safety of autologous nasal chondrocyte–based tissue-engineered cartilage for the treatment of OA cartilage defects in the knees of two patients with advanced OA (Kellgren and Lawrence grades 3 and 4) who were otherwise considered for unicondylar knee arthroplasty.
Post implant, the 34- and 36-year old recipients had less pain, better quality of life and radiological signs of joint recovery, with one patient showing increased space between knee joint bones on MRI.
No adverse reactions were recorded, and patients reported reduced pain as well as improved joint function and life quality 14 months after surgery.
“Our results have enabled us to lay the biological foundation for a therapy, and we are cautiously optimistic,” said Professor Martin.
“Unlike the cartilage tissue in the joints, these cartilage cells originate from precursor cells of the neuroectoderm and therefore have a distinct regenerative and adaptive capacity (plasticity). Tissue grown from nasal cartilage cells seems also to retain these special properties, he explained.
“Together, our findings indicate that N-TEC can directly contribute to cartilage repair in osteoarthritic joints. A suitably powered clinical trial is now required to assess its efficacy in the treatment of patients with OA,” they study investigators concluded.
The implants’ efficacy and safety will be further assessed in Swiss clinical trials, beginning in 15 knee osteoarthritis patients and expanding to 64 if successful.