Fix Knees With Fat

Fat…we Americans have an interesting outlook on it. In one sense it's nearly a dirty word, but, at the same time we've become marred by an epidemic of obesity.

Dr. John A. Szivek and his research team at the University of Arizona's Arthritis Center might give us all a new way to look at fat—as a source of stem cells and a treatment for osteoarthritis pain resulting from cartilage damage.

Osteoarthritis affects nearly 30 million adults reports the CDC (Center for Disease Control), with cartilage breakdown being one of the main reasons for pain. Total knee replacement is the standard of care for treating osteoarthritis in the knee, but there are significant drawbacks, namely that the diseased and, usually, the entire joint is replaced even if only part of it is damaged. How can you target healing in one particular spot of the knee, while leaving the healthy parts well enough alone?

Well, regeneration of the cartilage is the recurring dream. Enter Dr. Szivek who is turning to stem cells in fat as the solution for re-growth.

Why Fat?

The idea of using stem cells from fat for regeneration is actually not new, dating back to the late 1990's, when investigators studying cardiovascular tissue regeneration began employing cells from fat tissue. "The more difficult part is extracting them and preparing them specifically for orthopaedic applications, " explains Szivek, "and convincing the cells to form the right kind of tissue." Szivek says that typically if you place the stem cells on cartilage tissue or with other cartilage cells, they transform into cartilage cells, but getting them to form the right kind of cartilage is the hard part.

Fat cells can only produce fat tissue, but there are other cells in fat tissue because of the number of blood vessels in it, with stem cells being found in the lining of the blood vessels

"Joint cartilage is a highly organized, highly stratified tissue and the cells need to follow that pattern otherwise you end up with a fibrocartilage that is too flexible and weak." Not good for knees.

But how does this method differ or even outperform current methods, like using autologus cartilage cells collected from the patient? Szivek says that stem cells collected from fat is a lot cheaper and easier to obtain and prepare. (We all have a little extra hanging around.) "And [with autologus cartilage cells] it's difficult to get those few cartilage cells that can be collected safely to divide to the point where you have the 10, 000, 000 cells…." (The quantity needed to grow such complex forms of cartilage tissue.)

So what are the main benefits to using fat tissue to harvest stem cells? Well let's look at how stem cells are typically collected. Bone marrow is the go-to source for mesenchymal stem cells and that requires harvesting from the patient’s living bone (generally the iliac crest). Contrast that to harvesting fat tissue, which can be collected in a similar fashion to cosmetic liposuction (more on the possibilities here later).

The cells are plentiful in fat even in older patients, " says Szivek. "5 to 10 grams will provide between millions and tens of millions of cells. They can even be harvested from around the kneecap so it could be possible to do everything with one incision during surgery.

In Szivek's work standard lab equipment is used to extract the cells, but he says more efficient methods are definitely on the development horizon. "There are already a few companies that have developed completely automated enclosed 'boxes' that will process tissue in the operating room. The advantage of using an automated system is that it's faster and more reproducible." He adds this method promises a single, efficient procedure. "Extract the fat, take out the cells and then place them into the knee." Although Szivek has been in contact with two if these "box" developers, neither is approved for use in the U.S. for orthopedic applications at this time.

From Fat to Cartilage

If you guessed that scaffolding would be the next step in the process after the cells are extracted, you'd be right. Szivek's team developed a special scaffold that was created with the use of 3D CT scans. A patient's bone structure can be imaged and recreated in the scaffold. "The scaffold we are using has a structure that mimics the shape of the bone adjacent to the cartilage in a particular joint and we have primarily developed this type of scaffold so that we can replicate the compliance or springiness of the patient's bone. This allows us to accurately collect load measurements through the cartilage, " says Szivek.

Strain Gauged Scaffold/ Dr. John Szivek"Our implantable sensors and radio transmitter systems are the only ones in use to measure loads from tissues in situ, " says Szivek. The device, which looks like a smart phone, consists of a transmitter in the interior of the scaffold and a portable receiver. It measures the types of loads cartilage normally experiences when patients exercise, but could also offer clues to the best rehabilitation methods for cartilage tissue growth. Szivek says this is the first time a monitor like this is being used to measure loading in living tissue.

At the moment Szivek says this type of "focal defect repair" is currently being targeted to the younger patient demographic, however the long-term goal is to "be able to resurface an entire damaged surface, " particularly for those suffering from osteoarthritis. If this works out, the result could be fewer total knee replacements.

Get Better Knees and Get Skinny All at Once?

We couldn't help but wonder, given the connection to fat here, what the possibilities for a procedure like this could be. Obesity affects a large number of Americans each year—around 34% of the population according to Prevalence and Trends in Obesity Among U.S. Adults, 1999-2008 published this year in the Journal of American Medical Association. And with those numbers come obesity-related orthopedic issues, particularly in the knees. A Canadian report that looked at 2003-2004 joint replacements found that only 18% of joint replacement patients had what was considered an acceptable weight, with nine out of ten knee replacements patients being either overweight or obese. "That extra weight can be very damaging to an artificial joint since activities such as rising from a chair or climbing stairs can put up to five times your body weight onto your knee joints. As it turns out artificial knees do wear out more quickly if a patient is heavy, " adds Szivek.

Hand-held Computer and Receiver monitor/Dr. John SzivekSo it's obvious…fat generally isn't a good thing for joint health. But could we come to the point where the joint and weight problems were solved together? If you are a doctor performing a liposuction procedure to harvest stem cells, why not go further and take away additional fat? A thinner frame will ultimately figure better for the patient's joints, right? How does the line then become blurred between orthopedic and cosmetic surgeons? This isn't the first time the two practices have hybridized and the future should be interesting in this field.  

Patients have already been lobbying me to show that more fat removal is better, " adds Szivek, "so that these two procedures could be combined. At the moment we only use 5 to 10 grams of fat (about the size of a golf ball). More tissue means more cells and more cells may be useful.

Outcomes and Outlooks

Szivek says his team has observed no cartilage tissue when no cells are used with their scaffold and "appropriate cartilage tissue formation on some of our scaffold systems when stem cells are used." In one case Szivek says the engineered tissue was indistinguishable from the surrounding native tissue. "In addition, we have been able to measure loading during walking, running, jumping, crawling and stair. Although we have taken measurements from patients in other applications we have not yet collected measurements from the knees of human patients."

The University of Arizona team has just begun processing the human tissues for cell culture using an FDA-approved clean room and chemicals. "Assuming these cells respond as well as the ones we have used in our model we will be able to ask the FDA to allow preliminary testing in a patient model, " adds Szivek.