Got Knee Problems? Help May Be Up Your Nose (123RF) 800 × 524

Maybe it’s a matter of age. Maybe it’s just the people I hang out with. But in the last few years, almost everybody I know complains about knee pain. The vast majority of these painful knees are due to inflammation (arthritis), wear and tear from years of overuse, or injury caused by some sort of trauma. A frequent target of the overuse or injury is the meniscus, the cartilage that pads the ends of the bones of the knee joint. Without this padding, the ends of the bone rub against each other, and, as you can imagine, every step is agony.

 

What is cartilage?

Knee cartilage is a tough, rubber-like tissue. This property is important because it serves as the coating for the ends of the long bones of the leg. As such, it is subjected to constant stresses of compression, torsion (twisting), and friction.

Cartilage is basically connective tissue, just like bones and skin, but its unique molecular composition makes it an ideal padding. Skin and bone are made of collagen type I; cartilage is composed of collagen type II. Type II is different from type I in both its chemical structure and its capacity to hold on to water molecules. Cartilage also contains large aggregates of proteins that are “decorated” with long chains of sugars (glycans) that, in turn, hold on to large amounts of water molecules. The end result is a tough, rubbery gel with water filling the holes in the gel matrix.

This unique tissue is synthesized by specialized cells called chondrocytes. Once they finish their job, the knee chondrocytes just sit there, surrounded by the cartilage they created, pretty much performing the bare metabolic minimum to survive. In fact, the whole tissue is pretty much inert: no blood supply, no nerves, nutrients reaching the cells by the very slow process of diffusion. So it is not surprising that, unlike other tissues, there is no repair of injured cartilage. After years of wear and tear, either through trauma or inflammation (arthritis), the cartilage is simply worn away.

 

What can be done?

First, let me tell you what doesn’t work. Supplements of glucosamine/chondroitin are a total waste of money. The reason is obvious. Cartilage is synthesized by the chondrocytes, and once they cease their synthetic activity as I described, no more new cartilage is created. Period. The supplements, even if a minuscule amount manages to reach the joint, are totally useless as substitutes for cartilage tissue.

Clinically, the only effective treatment, short of replacing the knee with a prosthesis, is arthroscopic lavage and debridement. Basically, it consists of removing the damaged and degenerative cartilage.

The surgical approach has its limits. The procedure is palliative only; there is no regeneration of new tissue to replace the old. A review of the literature found that knee surgery is ineffective at reducing joint pain or improving joint function in people with osteoarthritis. The researchers did, however, find that arthroscopic surgery helped a minority of patients with milder symptoms, large tears, or other damage to the cartilage.

 

The biological approach

Now that we know how to grow stem cells of different tissues in the lab, why not make new cartilage in the lab and then implant it in the damaged joint? Unfortunately, this was tried but was largely unsuccessful. The joint chondrocytes were simply too inert to produce sufficient amounts of new cartilage.

A recent paper published in the British medical journal, The Lancet, is a real breakthrough. The scientists from the University Hospital Basel obtained chondrocytes from the nasal septum, which separates the left and right airways in the nose, dividing the two nostrils. These chondrocytes make a lot more cartilage in culture, and more reproducibly than knee cartilage. They took a 6mm nasal septum biopsy from each of 10 patients who had trauma-induced cartilage lesions. After allowing the chondrocytes to make new cartilage tissue in the lab, they implanted the engineered tissue in the respective joint defects. 

The patients were followed for up to 24 months. On the molecular level, the implanted cartilage gradually assumed the composition of joint cartilage. Clinically, no adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery compared with 24 months after surgery. Radiological assessments indicated variable degrees of defect filling and development of repair tissue approaching the composition of native cartilage.

 

The bottom line

Although this was a small study (10 patients initially, but expanding now to 25), the results are so impressive that I hope it will quickly be replicated in the U.S. And if successful, gain rapid approval from the FDA so that it can quickly get to market. It would be an enormous breakthrough for the millions of souls suffering from chronic, debilitating knee pain.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.

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