In a small trial of 10 patients with damaged knee joints, doctors harvested cells from their noses to engineer new cartilage tissue and transplant it into their damaged knees. In a paper published in The Lancet, the Swiss team describes how 2 years after transplant, most of the patients had developed new tissue similar to normal cartilage and reported improvements in knee function, pain, and quality of life.
However, the authors point out that while the results of their phase I study are promising and show the approach is feasible and safe, there is still a long way to go before such a procedure can be approved for routine use with patients.
They note that the observational study only involved a small number of patients, there was no control group, and the follow-up was quite short.
There now needs to be randomized trials – with longer follow-up – that compare the promising treatment with conventional alternatives.
Lead author Ivan Martin, professor of tissue engineering at the University of Basel and University Hospital Basel in Switzerland, adds:
“Moreover, in order to extend the potential use of this technique to older people or those with degenerative cartilage pathologies like osteoarthritis, a lot more fundamental and pre-clinical research work needs to be done.”
About 2 million people in Europe and the United States are diagnosed with damage to knee joint cartilage every year, caused by injury or accident.
Joint or articular cartilage is the layer of smooth tissue at the ends of bones that eases movement, and protects and cushions the surfaces of the joint where the bones meet.
As this tissue has no blood supply, if it gets damaged it cannot regenerate. Eventually, as the cartilage wears away, the bones become exposed and inflamed from rubbing against each other, leading to painful joint conditions like osteoarthritis.
There are medical techniques – such as microfracture surgery – that can prevent or delay the onset of cartilage degeneration following injury or accident, but they do not regenerate healthy cartilage to protect the joints.
There have also been attempts to use cartilage cells or chondrocytes from the patients’ own joints to make new cartilage in the joint, but these have not been very successful at creating the right structure and function of the cushioning tissue.
One of the unique features of the new study is that Prof. Martin and colleagues used chondrocytes harvested from a site far away from the damaged joint – from the patients’ nasal septum. These cells have a unique ability to grow new cartilage tissue.
For the study, the team enrolled 10 patients (age 18-55) with full-thickness cartilage damage to the knee and took a biopsy from their nasal septum under local anesthetic. They grew chondrocytes harvested from the biopsy tissue by stimulating them with growth factor for 2 weeks.
The team then took the cultured new cells and seeded them onto “scaffolding” made of collagen and grew them for another 2 weeks. The result was a 2-millimeter thick graft of new cartilage measuring about 30-40 millimeters.
Each patient then underwent surgery where the damaged knee cartilage was removed and replaced with their own cultured graft cut into the appropriate shape.
After 2 years, scans showed new tissue of similar composition to cartilage had grown at the affected sites.
Nine of the 10 patients – one was excluded because of sports injuries not related to the trial – also reported significant improvements in the use and function of their knee and reduction in pain, compared with pre-surgery.
The authors note there were no reports of adverse reactions to the surgery, although there were two reports of injuries not related to the procedure.
In an accompanying comment article, Dr. Nicole Rotter, from Ulm University Medical Center, and Dr. Rolf Brenner, from the University of Ulm – both in Germany – say the trial “represents an important advance towards less invasive, cell-based repair technologies for articular cartilage defects.”
The main reason they give is that the cells were not taken from healthy tissue near the site of injury but from a completely unaffected part of the body, which avoids the risk of harvesting affecting the damaged joint.
They also mention the promising result that patient age does not appear to affect the success of the procedure.
However, like the trial authors, they conclude that only longer-term randomized, controlled trials – that among other things test the quality of the repair tissue – will be needed before we can say whether this approach is likely to gain regulatory approval and reach clinical use.
“Our findings confirm the safety and feasibility of cartilage grafts engineered from nasal cells to repair damaged knee cartilage. But use of this procedure in everyday clinical practice is still a long way off as it requires rigorous assessment of efficacy in larger groups of patients and the development of manufacturing strategies to ensure cost effectiveness.”
Prof. Ivan Martin