Cell Therapy for Cartilage Repair: A Review and UpdateResearch into repair techniques for damage to knee cartilage is moving right along. Surgeons in Europe and Australia are ahead of American surgeons as they have moved from first-generation cartilage repair through second generation methods to the more current third-generation approaches.
Only one type of third-generation cell therapy for cartilage repair is available in the United States: the matrix-induced autologous chondrocyte implantation or MACI. MACI is the subject of this review article. Although it is being used by U.S. surgeons, the U.S. Food and Drug Administration (FDA) has not yet approved this type of cell carrier yet.
But let's step back a minute and get some background information that will help you understand what's going on. The basic problem is one of damage to the articular (joint surface) cartilage of the knee. The hole or defect can be small but deep (all the way down to the bone). Sometimes, the defect is large (wide and deep).
The affected person experiences knee pain and joint swelling, locking, stiffness, and clicking. The symptoms can be bad enough to interfere with daily activities at home and work and create quite a bit of disability. Sports participation can be out of the question.
Because so many athletes are affected and given the fact that knee joint (articular) cartilage doesn't repair itself, researchers started looking for ways to treat cartilage injuries of this type. They tried scraping the area and smoothing it down, a procedure called debridement. They tried drilling tiny holes into the bone marrow to stimulate bone healing. That's called microfracture. And they tried taking healthy cartilage from one part of the knee and transferring it to the lesion to fill in the hole.
All of these treatment methods had problems. There wasn't one approach that could work well for all different types and sizes of cartilage defects. That's when cell therapy was developed. Healthy cartilage cells (chondrocytes) were harvested from the knee but instead of using them directly in the damaged area, they were transferred to a lab. In the lab, the cells were used to grow more cells. When there were enough cells to fill in the hole, they were reimplanted into the patient and covered with a patch made of periosteal (bone) cells.
That procedure was called autologous chondrocyte implantation (ACI). It was the first cell therapy devised for the problem of full-thickness (down to the bone) cartilage injuries. That's why it's considered a first-generation approach to cell therapy cartilage repair. But again there were problems. The procedure is invasive and requires a two-step (staged) surgical procedure. That means at least two surgeries with all of the possible costs and risks that go with staged procedures.
The next batch of autologous chondrocyte implants were improved and formed the second-generation techniques. Instead of covering the patched up hole with periosteum (bone cells), they tried using a collagen covering. The idea was to prevent overgrowth and keep a smooth surface. Overgrowth of bone called hypertrophy was a real problem with the periosteal patch.
Not quite satisfied that the second-generation approach was the best they could do, scientists continued trying different ways to improve cell therapies. The result was the current third-generation: using a three-dimensional scaffold or frame upon which to grow new cartilage cells. This is the procedure that's called the matrix-induced autologous chondrocyte implantation (MACI).
MACI is still a two-step procedure that starts with the harvesting of healthy chondrocytes that are then taken to the lab to reproduce. Only this time, they are placed directly onto the scaffold that is made of type I and III collagen tissue. When the transplanted cells (taken from the patient's body) have reproduced enough (in the lab) to fill in the gaps on the collagen scaffold, then the patient returns to the operating room and the MACI implant is cut to fit the defect and glued in place.
The question this report tries to answer is how well is this third-generation method of cell therapy working to repair damage to the articular cartilage of the knee? Over 6000 MACI implants have been completed (outside the U.S.). Reports have been trickling in over the last 10 to 12 years so the authors reviewed all the published studies and compiled this summary.
Most of the 12 studies that met the requirements for high-quality were case series or case reports (not large randomized, controlled studies). Only one randomized controlled trial was found but in all cases, patients reported significant improvements in pain, function, and activity level. Measurable results based on patient report and MRI studies were seen as early as three months after surgery but more often the benefits occurred during the first year. Post-operative complications were rare and included infection, detachment of the transplant, and overgrowth of the graft.
In summary, matrix-induced autologous chondrocyte implantation (MACI) is a less invasive, third-generation cell therapy treatment technique that has improved on first and second-generation methods of cartilage repair. Surgical time is shorter because there's no need for a periosteal flap or microsuturing the implant in place (remember they use glue instead). Quality of tissue repair is good and the procedure appears to be safe.
So far, all we have are short-term results. Future studies will continue to report data that will further reflect the long-term results of MACI. Moderate-to-large cartilage defects can be repaired this way. Affected individuals (especially athletes) are able to get back to an active lifestyle, including full sports participation.
Mats Brittberg, MD, PhD. Cell Carriers as the Next Generation of Cell Therapy for Cartilage Repair. In The American Journal of Sports Medicine. June 2010. Vol. 38. No. 6. Pp. 1259-1271.
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