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You are here: Home / Articles / New Methodology to Improve Cartilage Repair

New Methodology to Improve Cartilage Repair

July 31, 2013 • By Lara C. Pullen, PhD

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Successful autologous chondrocyte implantation (AIC) is not yet possible due to the dedifferentiation of chondrocytes during cell expansion. A new study finds that a single treatment with recombinant acid ceramidase (rAC) improves the chondrogenic phenotype of primary chondrocytes. The authors also report that a single in vitro treatment of rAC leads to an increased yield of mesenchymal stem cells (MSCs) at one week.

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Calogera M. Simonaro, PhD, and colleagues at Mount Sinai in New York City, published the results of their study of rAC in PLoS ONE.1 The finding represents “a new way to grow chondrocytes and improve the outcome, hopefully, of cell-based cartilage repair,” says Edward H. Schuchman, PhD, principle investigator of the study.

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The authors found that administration of rAC results in short-term changes of sphingolipid metabolism that may ultimately result in long-term effects on the chondrogenic phenotype. They speculate that the resulting changes in sphingolipid metabolism led to transcriptional and posttranslational modifications.

Cartilage repair is an area of active research, and two candidate strategies top the list: AIC and MSC. Currently, Genzyme is the only company in the U.S. approved for preparing these cells for implantation. The new findings suggest that rAC could have a positive effect on both of these treatment strategies.

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The result could be an important advance in cell-based cartilage repair through the production of higher-quality cells for transplantation. Genzyme is currently evaluating the effects of rAC in their culture system and determining whether or not rAC improves clinical outcomes with their cells.

Dr. Simonaro and Dr. Schuchman are co-inventors of a patent application describing the use of rAC in chondrocyte differentiation. The enzyme is currently only being manufactured on a small scale in Dr. Schuchman’s laboratory. Dr. Schuchman tells The Rheumatologist that much work still has to be done to create a clinical grade, commercial enzyme.

As a geneticist, Dr. Schuchman began his rAC research by studying patients with Farber disease. These patients have a deficiency in acid ceramidase and are therefore unable to break down cellular fatty acids. The lipids accumulate throughout the body and cause abnormalities in the joints, liver, and elsewhere. Children with Farber disease may first be referred to rheumatologists due to their joint abnormalities.

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“We knew from that proof of principle that the enzyme was very important for cartilage repair,” explains Dr. Schuchman. He hopes that a commercially available enzyme will also be able to relieve symptoms of Farber syndrome.

Pages: 1 2 | Single Page

Filed Under: Conditions, Research Reviews Tagged With: cartilage, cartilage repair, chondrocytes, mesenchymal cells, recombinant acid ceramidase

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