No evidence autologous chondrocyte implantation is superior to conventional techniques

Duplicated data, limited blinding, heterogeneous designs and short follow-ups hamper thorough review, authors say.

Sifting through a decade of clinical data tuned up no evidence that autologous chondrocyte implantation is more effective than conventional techniques for treating chondral knee lesions, two researchers found. ACI is safe, however, and produces few side effects, they said.

Researchers A. Ruano-Ravina, PhD, and M. Jato Diaz, MD, of the Galacian Agency for Health Technology Assessment, Galacian Department of Health in Santiago de Compostela, Spain, reviewed clinical studies and case series published between January 1994 and December 2004. Their findings appeared in the January issue of Osteoarthritis and Cartilage.

Autologous chondrocyte implantation (ACI) is a two-step procedure. Step one involves harvesting wafers of articular cartilage and culturing chondrocytes for implantation. In the second arthroscopic step, surgeons cover the chondral lesion with a periosteal flap sutured to the surrounding cartilage. Then they inject cultured chondrocytes under the flap, which is sealed closed.

Study scarcity and limitations

Published clinical data on ACI are scarce. The clinical and case studies Ravina and Diaz reviewed had various shortcomings including the following:

short follow-up times;
limited blinding (because of ACI having two steps), heterogeneous designs;
redundant data (several studies coming from the same groups); and
nonstandard techniques or indications.

Ravina and Diaz reviewed three clinical trials and nine case studies. They chose studies with more than 20 patients and that measured clinical, histological and/or lifestyle outcomes, excluding in vitro and animal studies.

Three randomized clinical trials compared ACI with microfracturing, osteochondral cylinder transplantation and mosaicplasty. Knutsen’s 2004 study included 80 patients and compared ACI with microfracturing. Both techniques showed similar clinical outcomes after two years. Patients who had undergone microfracture had better lifestyle outcomes at two years, however. Also, patients younger than 30 years had better clinical outcomes.

Knutsen, presenting the same study at the International Cartilage Repair Society 2006 Meeting, showed no differences between the groups at five years’ follow-up.

Among the case studies, Peterson and Minas’ 2003 paper showed 91% of patients having good or excellent outcomes, with one reported graft failure at two years. Minas’ 2001 study of 169 patients treated between 1995 and 1999 showed “significant” lifestyle improvements at two years among patients with the most complex lesions. Only 13 patients had graft failures.

“In conclusion, although ACI is a safe technique, available data are not indicative of its being more effective than other therapeutic strategies in the treatment of chondral lesions of the knee,” the authors wrote. “Moreover, ACI is a relatively costly procedure, since it requires two interventions and cell culturing in vitro. These considerations place ACI at a disadvantage when compared to conventional techniques.”

Ongoing ACI research

One leading orthopedic surgeon vouched for the lack of evidence showing ACI’s efficacy but voiced hope that new techniques will move cartilage repair forward.

“New techniques of ACI are being developed,” said Freddie Fu, MD, a member of the Orthopedics Today Editorial Board and an orthopedic surgeon practicing at the University of Pittsburgh Medical Center.

For example, matrix-induced ACI (MACI), with chondrocytes coated in a collagen membrane, and use of a hyaluron membrane make arthroscopic chondrocyte implantation possible, Fu said. “However, [new techniques] are still costly, require two surgical interventions and there is no study comparing the outcomes of these new techniques with other techniques.”

Still, ongoing research promises to yield more technological advances, Fu said.

“Several experimental studies of tissue engineering and gene therapy have been performed in order to better restore the cartilage,” he said. The experimental treatments include new polymers with cells and growth factors and engineered cells that may help inhibit cartilage deterioration or enhance cartilage formation, he said.

For more information:
Ravina AR, Diaz, MJ. Autologous chondrocyte implantation: a systematic review. Osteoarthritis Cartilage. 2005;14:47-51.