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In osteoarthritis of the knee, the cartilage that should cushion the bones erodes, leaving people in pain. Anti-inflammatory drugs may provide some relief, but they cannot cure the condition or bring back the already lost cartilage. Joint replacement allows people to move again, but their implants eventually need to be replaced.
A possible solution could be found in a person’s nose. Ivan Martin, head of biomedicine at the University of Basel and University Hospital Basel, and his colleagues led a study published Wednesday in Science Translational Medicine that reports on the bioengineering of nasal chondrocytes – cells that form cartilage – and implanting them in the knee to grow new cartilage. and is more resistant to inflammation than the original cartilage in the knee. He studies three-dimensional cell culture systems to understand how tissues develop, how to control tissue formation, and how to turn lab-generated tissue into possible grafts for tissue repair.
Martin spoke to STAT about his team’s work, which has gone from lab dishes to mice, sheep, and ultimately two patients. This interview has been edited and condensed for clarity.
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When did you set your sights on osteoarthritis of the knee?
It took us, say, 15 years to learn every possible adjustment to be able to generate modified human cartilage tissue in a three-dimensional size and shape with certain functional properties. Once we learned how to generate these grafts, we started implementing them in clinical studies for different indications.
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What steps did you have to take to get there?
We had to study how these modified cartilage tissues would behave in an environment different from their native origin. And so for the knee joint, we had to conduct different studies, in vitro and on animal models, to understand if these cartilages would also be compatible with an implantation in a joint.
What’s the take-home message from your journal?
Our research indicates that this modified cartilage is not only able to regenerate cartilage tissue, but is also resistant to signals of inflammation, which are usually very high and strong in a degenerated joint like those of patients with osteoarthritis. So this cartilage is actually able to counter it, reduce inflammation in the joint.
Did you expect the bioengineered nasal tissue to behave the way it did? And why does it work better than knee tissue?
It was quite surprising. But then we identified that nasal cartilage cells have a certain gene signature typical of neural crest cells, from which our hierarchically higher organs, like the eyes or the brain, derive. Coming from this compartment, these cartilage cells in the nose have a higher regenerative capacity than cartilage cells in a joint – and also a higher plasticity, therefore the ability to adapt to a different environment.
Have people tried this before?
In the past, especially for the regeneration of cartilage, what the domain has done and still does is take cells from the same joint, therefore joint cartilage cells, and develop them and inject them into the same articulation. We use a different source of cells and organize these cells into functional tissue before implantation. So we are not injecting a suspension of cells, but we are injecting an effective cartilage tissue.
What does the procedure look like?
First, we take a small biopsy of the nasal septum, a few millimeters in diameter, under local anesthesia. From this small tissue, we isolate the cells and grow them in the laboratory. And once we have enough – it takes about two weeks – then we load them onto a transporter. It’s a sponge made of collagen and we let them colonize the sponge and mature and develop new tissue, which takes another two weeks. So after a total of four weeks we have this mature cartilage tissue that we implant into the patient.
How long do you think this new cartilage could last?
Let’s be realistic. In these two patients, the implanted cartilage prevents them from having to undergo total knee replacement surgery. But we don’t know in the long run what will happen. What we are considering is the possibility of a combination therapy. So, where this artificial cartilage is implanted in the knee and is resistant and reduces inflammation, at the same time, we want to take care of a root cause of cartilage generation, correcting it surgically in some patients. We may need to introduce simultaneous pharmacological treatment, or we may just have to be very careful with targeted physiotherapy, which we know is very important.
How long have their implants been?
They have been followed for more than two years now.
Are you focusing on osteoarthritis, not rheumatoid arthritis?
We target osteoarthritis where inflammation is not the cause of osteoarthritis, but there is another cause that leads to inflammation, such as, for example, abnormal load in the joint. It is not general osteoarthritis either. These two patients suffer from so-called medial osteoarthritis [affecting the middle of the knee]. The next target is femoropatellar osteoarthritis [affecting the kneecap and part of the femur].
What else is next?
There are several progressive stages. The first is to pursue other clinical studies in a larger cohort. We need to expand it to a clinical trial of appropriate power with a control arm to demonstrate efficacy.
Was it difficult to create this bioengineered tissue implant?
Yes. That’s why it took us 15 years of preclinical work.
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