The Food and Drug Administration (FDA) recently approved a new product to repair damaged knee cartilage using cells from the patient’s own knee. The product, called Matrix Associated Chondrocyte Implantation (MACI), is approved for use in people younger than age 55 who have what are known as “focal chondral defects,” which can be a precursor to knee osteoarthritis (OA). Experts say, while MACI is not for use in people with knee OA, it does provide a new treatment option to prevent OA from developing in a particular group of patients.
Focal chondral defects are cartilage lesions that often occur in younger people and usually are related to some type of injury, explains John Hardin, MD, professor emeritus in the department of orthopedic surgery at Albert Einstein College of Medicine, in the Bronx, NY.
“A small region of cartilage is crushed and falls apart, and you’re left with this bare, denuded bone that’s very painful,” Dr. Hardin says. “There has not been a good, satisfactory, reasonably reliable way to manage these cartilage defects. So something that advances the treatment is a really welcomed thing.”
Focal Chondral Defects Are Like Potholes
Focal chondral defects can be considered an early stage of osteoarthritis, says Christian Lattermann, MD, director of cartilage repair and restoration at University of Kentucky Health Care in Lexington and a consultant for Vericel, the company that developed MACI. However, not everyone who has OA started out with a focal chondral defect. “There is a flowing continuum of joint disease that [can] start with an early injury… then gradually progresses toward focal chondral defects, then continues on to changes on X-ray that constitute formal osteoarthritis,” he explains.
MACI is a third-generation cartilage repair technology. It’s preceded by autologous chondrocyte implantation (ACI), which has been around since 1997, and before that by microfracture, which has been around since the 1980s. Dr. Latterman has been performing ACI for years and worked with Vericel as it developed the MACI technology. During testing, they learned that MACI should not be used in people with end-stage knee OA because it will not likely have satisfactory results in the mid or long term.
Farshid Guilak, PhD, an expert in the field of regenerative medicine for osteoarthritis, explains it this way: “Imagine a road and you have a pothole in the road. That’s what MACI is good for. But with OA you need to repave the entire road, because everything is degenerated. The joint as an organ is diseased – the synovium is inflamed and cartilage is affected everywhere in the joint.” Guilak, co-director of the Washington University Center of Regenerative Medicine in St. Louis, Missouri, was not involved in the development of MACI.
How MACI Works
During an arthroscopic examination of the knee, the surgeon cleans debris out the knee, determines the size of defect and decides if the patient is a good candidate for MACI. If the person is a good candidate, the surgeon removes a piece of cartilage about the size of two Tic Tacs from an area of the knee that is not weight-bearing.
The cartilage sample is sent to a lab where the chondrocyte cells are isolated, seeded onto a membrane, and grown under special conditions for two to three weeks. The complete MACI patch is shipped back to the surgeon, who then implants it into the defect. The whole process takes two to three months.
Dr. Latterman says MACI is an improvement over the older ACI procedure with regard to the ease and extent of surgery required, since the chondrocytes already come seeded onto a scaffold that the surgeon can use directly to patch the defect.
In the MACI studies, the average size defect that was filled was less than a square inch. About 85 percent of implants survive, grow, fill the cartilage void and mesh with the existing cartilage.
Future Outlook for Cartilage Repair
Dr. Lattermann explains that MACI is the first of these third-generation cartilage repair technologies to be approved for use in the United States, but several others are in the pipeline that will hit the market over the next several years.
Right now, all of these procedures are for focal chondral defects, not osteoarthritis. “The field is expanding more and more to try to treat osteoarthritis patients earlier and earlier,” Dr. Latterman says. “The future will be a combination of earlier detection, earlier nonoperative intervention, and earlier operative intervention.”
Guilak agrees that early intervention is key, but says of OA repair, “If you want to treat osteoarthritis, you have to treat the entire cartilage surface as well as the rest of the joint. If you have degenerative processes going on, any new tissue you put in there will also get degraded, just as the native tissue got degraded.” He predicts that in OA, anti-inflammatory drugs would be needed to protect the new cartilage if it’s implanted into an inflamed joint.
Guilak, who has received Arthritis Foundation funding for other research, says the solution to cartilage repair for OA isn’t clear-cut. He and his research team are tackling the same problem, generating new cartilage tissue, by using a different method: fat-derived stem cells. “Autologous chondrocytes [like those used in MACI] will make cartilage, but you have to harvest them from somewhere else in the joint, so you end up damaging cartilage,” he says.
His team’s approach also has challenges. “Stem cells have to be differentiated into chondrocytes to make cartilage, but they are available in much larger numbers without damaging your native cartilage,” he explains. “So the long-term solution isn’t clear yet, and there may be more than one solution.”
In addition to Dr. Guilak and team’s research work, the Arthritis Foundation is also funding other teams looking to regenerate cartilage. You can check out the work of Dr. Veronique Lefebvre here.
Beth Axtell, for the Arthritis Foundation