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CARTICEL® (autologous chondrocyte implantation, or ACI)

I’ve got good news and bad news …

1,600 words, published 2009
by Paul Ingraham, Vancouver, Canada

CARTICEL® is the brand name for a new surgery to repair knee cartilage. The concept is called “autologous chondrocyte implantation” (ACI) — implanting your own cartilage cells — and it depends on some biotech wizardry owned by Genzyme Corporation. Genzyme is the world’s third largest biotech company, and massive biotech companies make a lot of people feel nervous; Genzyme, however, has thus far been an admirable corporate citizen, and is reputedly an excellent company to work for. For better or for worse, it takes Genzyme-scale resources to develop and deliver a technique like ACI — this is Big Medical Science.

Genzyme takes a small sample of your very own cartilage cells (chondrocytes) and grow them into a surplus population of several million spares that a surgeon implants back into your knee. This is somewhat like tossing some grass seed on a rough patch of lawn, only it requires a bunch of folks with advanced degrees, and it costs USD $20,000–35,000 (which will probably come down). Genzyme is still working on the ideal formula for getting the implanted cells to stay put and make new cartilage, and there are probably upgrades in the pipeline. The limitations of Carticel today may not be the limitations of the Carticel of tomorrow. Here’s a YouTube video of a surgeon performing the procedure:

For my readers — particularly many of you who have chronic patellofemoral pain syndrome (kneecap pain) — I’ve got good news and bad news about Carticel and ACI. It’s both miraculous and limited.

It takes Genzyme-scale resources to develop and deliver a technique like ACI — this is Big Medical Science.

On the bright side, there seems to be little doubt that the Carticel procedure can grow new cartilage. Marvellously, the implanted cells produce fresh, shiny new cartilage! Which is pretty cool! I defy anyone to be unimpressed by that.

Cartilage just doesn’t fix easily. In the past, trying to repair degrading cartilage with surgery has involved comparatively primitive methods: polishing it (debridement); trying to stimulate healing with stresses, such as creating tiny fractures in the underlying bone (microfracture), or drilling or abrading it (drilling/abrasion); transplanting chunks of bone and cartilage from somewhere (or someone) else (autograft/allograft). None of these techniques has a particularly good track record. By contrast, implanting cells seems awfully clever and advanced.

And the patient gets “sustained and clinically meaningful improvement in pain and function,” according to American Journal of Sports Medicine in January of 2009 (plus other, similar research results reviewed below). It all sounds pretty great, and makes me want to buy GENZ!

ZOOM
Chondrocytes: the cells that build and maintain cartilage: The sparseness of chondrocytes scattered throughout cartilage mean that your joints are “plagued by inherent limited healing potential.”

Chondrocytes: the cells that build and maintain cartilage

The sparseness of chondrocytes scattered throughout cartilage mean that your joints are “plagued by inherent limited healing potential.”

ZOOM
Chondrocytes: the cells that build and maintain cartilage: The sparseness of chondrocytes scattered throughout cartilage mean that your joints are “plagued by inherent limited healing potential.”

Chondrocytes: the cells that build and maintain cartilage

The sparseness of chondrocytes scattered throughout cartilage mean that your joints are “plagued by inherent limited healing potential.”

On the other hand, as always, you’re going to sober up after reading the fine print — as always. And I mean the literal fine print in this case — the Carticel website has a large batch of prominent fine print (is that a contradiction?) on every page, just like drug ads in magazines. And you can learn some pretty interesting things from that small print! Hands down the most interesting is that, although ACI is a treatment for regrowing cartilage, it’s not actually intended for arthritis: according to Genzyme Corporation, “It is not indicated for the treatment of cartilage damage associated with generalized osteoarthritis.”

Er, really? That’s quite a kick in the optimism. This is definitely not what most candidates want to hear. But it’s true: by design, ACI is currently intended only for younger patients with cartilage that has been damaged by injury. Why? Rehabilitation is not quick or risk-free. Even with a large batch of fresh chondrocytes, growing cartilage is slooooooow. There are also numerous potential complications, such as overgrowth of the implant — eek, it’s alive, and it’s taking over my knee! — which are more likely across the board for older patients.

Even with a large batch of fresh chondrocytes, growing cartilage is slooooooow.

So this procedure is actually not appropriate for the majority of (older) people with a lot of stubborn anterior knee pain, or even for large numbers of younger patients whose cartilage just isn’t rough enough to justify it.

In a word, bummer.

Genzyme’s slogan for their own product is remarkably restrained because of the various problems, the worst of which I haven’t even brought up yet: “the only treatment that uses your own cells to regenerate your knee cartilage that may offer a long-term solution for a knee cartilage injury.” May offer. May. Hmm …

Nicer cartilage is just not the same thing as cured knee pain

If only wishing made it so.

The <cite>American Journal of Sports Medicine</cite> has published three studies of AIC so far this year.

The American Journal of Sports Medicine has published three studies of AIC so far this year.

There have been three prominent studies of chondrocyte implantation this year that I know of, all of them in American Journal of Sports Medicine. The largest was the STAR study, published in January: the Study of the Treatment of Articular Repair, which was the source of the rather glowing results quoted above. Also in January, Kon found it was not only “satisfactory” but produced “better clinical results and sport activity resumption” than the microfracture technique; and Gobbi concludes that the treatment resulted in “a significant decline” in lesions and pain and is a “viable” treatment.

Indeed, ACI looks promising. Results from STAR and Kon et al seem to pretty decisively show that it is almost certainly an improvement over older techniques. However, there is an important caveat that would be easy for the casual student to miss …

All three studies show dramatic improvement in the patients’ knee cartilage, but they each also showed that patients did not recover completely from their knee pain. For instance, Gobbi et al’s subjects went from an athletic activity (Tegner) score of about 2.5 to about 4.75 — a level of activity that does not even include “recreational sports.” We’re talking about patients who are barely running or even playing beer league softball.

Or consider Kon et al’s subjects, who went from a subjective score of 41 originally to 70 five years later. That’s a nice improvement, but still well short of feeling fantastic. How “cured” of a chronic pain would you feel if you were only at 70% of healthy status? Most athletes don’t want to operate at much less than “110%” — 70% is still pretty broken as far as most seriously active people are concerned.

The STAR study had similar results: across the board, by several measures, results were a heck of a lot better than nothing, but also well short of full recovery.

We’re talking about patients who are barely running or even playing beer league softball.

So, patients who were treated with ACI definitely improved, and that is not an unimportant result. But cured? Not hardly! Despite the fact that their cartilage looks much nicer than it did, these patients are still not exactly good to go. Unfortunately, there are still more reasons for concern.

Does Carticel power a placebo?

Could the Carticel benefits found by researchers have been in the mind? It seems unlikely at first glance — this is cold, hard surgery we’re dealing with, and the results were strongly positive, “statistically significant” and all that. Unfortunately, a placebo effect is not an unreasonable consideration after a closer look. The value of uncontrolled studies of knee pain surgeries (and probably other many other surgeries) should always be suspect in principle, but especially since the surprising discovery (by Moseley) that a surgical placebo can act strongly on patients. For a summary of that fascinating bit of science, see Knee Surgery Sure is Useless!

Kon et al’s study was compared only to an older cartilage repair technique, and Kon et al did not compare their patients to anything at all. So neither of these surgeries was compared to a placebo, and that’s definitely a problem. Bizarre as it sounds, it’s actually quite plausible that a substantial benefits of the surgery were due to placebo.

The STAR study was larger, and it looked only at patients who had already failed to get relief from a previous, non-ACI knee surgery — a kind of compromise. If these patients already had surgery that had no effect, placebo or otherwise, it’s safer to assume that the ACI benefits were “real.” It’s safer, but still not safe: the cool-factor of a fancy new surgery can probably power a superior placebo. Remember, it’s been nicely proven that people like the taste of crappy wine when they think it’s the expensive stuff — they almost certainly think the price and über-modern cache of ACI means it must be more effective … and that absolutely has an effect on patient hopes, dreams, and placebos.

Although this is no more proven than anything else, it really is possible that the new surgery is no better than the old one: just better at generating a robust placebo effect. Crazy, eh?

If people like the taste of crappy wine when they think it’s the expensive stuff, then they will also think that the price and über-modern caché of ACI means it must be more effective

But the bottom line is always that patellofemoral pain is multifaceted

An even more obvious explanation for the imperfect results of the surgeries is this: the condition of your cartilage is only one of many factors in anterior knee pain. Patellar bone fatigue and synovial membrane irritation, for instance, are two other major candidates — and likely involved to some degree in many cases of knee pain.

As usual when I write about patellofemoral pain, this information will soon be integrated into my massive tutorial on the subject, and in time it will be available only to my customers.


Save Yourself from Patellofemoral Pain Syndrome!

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