BioWorld International Correspondent

LONDON - For the first time, researchers showed how to turn human embryonic stem cells into cartilage. In 10 years, it might be possible to grow cartilage for transplantation, in order to treat sports injuries, assist in joint replacement surgery and even grow new body parts for cosmetic surgery.

The scientists who carried out the work used a technique in which they grew the embryonic stem cells (ESCs) alongside chondrocytes (cartilage cells), so that growth factors from those cells could spread to the ESCs and stimulate them. They then placed those cells on a support, which they implanted in mice.

Archana Vats, an ear, nose and throat surgeon at St. Mary's Hospital and Imperial College in London, told BioWorld International, "Injuries that affect cartilage account for huge amounts of money spent by health services. Finding a way to generate an unlimited supply of cartilage, as we have done, has huge implications."

Vats and her colleagues reported their studies in the Nov. 16, 2005, issue of Tissue Engineering in a paper titled "Chondrogenic differentiation of human embryonic stem cells: The effect of the micro-environment."

To date, reconstruction of cartilaginous parts of the body involved taking cartilage from one place and transposing it to the injured area. Vats said, "Unfortunately this can cause problems for the region of the body where you take the cartilage from, and often there is not enough to allow you to carry out adequate repair or replacement."

The new method raises the prospect of being able to "grow" the desired amount of cartilage in the shape of an ear, a nose or the cartilaginous disc that lines a joint. That may be possible by taking cartilage cells from a patient, growing them with embryonic stem cells in the laboratory and then transplanting them back into the same patient.

Cartilage produced in that way would have a multitude of applications. It could help to reduce or delay the number of joint replacements that will be needed by the world's aging population. If surgeons could replace the worn-out cartilage on a joint, they might be able to delay the need for surgery or avoid having to replace the entire joint.

Many younger people with sports-related cartilage injuries also could benefit. So would those needing reconstructive work following surgery for head and neck cancer. Finally, there is the potential to repair noses and ears damaged through injury - or simply replace them for cosmetic purposes.

Vats and her colleagues used the established technique of indirect co-culture to encourage the ESCs to turn into chondrocytes. That involved growing the ESCs in wells, while dipping a "well insert" containing chondrocytes into each well.

The well insert is made from a permeable membrane that allows growth factors secreted by the chondrocytes to pass into the part of the well containing the ESCs.

Vats explained, "There is no physical contact between the two sorts of cells, but we hypothesised that signals produced by the chondrocytes would be able to induce the ESC to differentiate toward the chondrocyte lineage."

Tests on the ESCs showed that the cells were able to develop into mature chondrocytes. Those ESCs grown in co-culture with chondrocytes had higher levels of collagen - the protein constituent of cartilage - than ESCs grown without chondrocytes.

Once the ESCs developed into chondrocytes, the well inserts were removed, and the remaining cells were placed on a three-dimensional material called a bioactive scaffold.

Vats said, "This bioactive scaffold has an architecture that is designed to encourage tissues to grow, including blood vessels. It is necessary in order to help the cartilage grow into a three-dimensional structure, such as the meniscus of the knee joint - otherwise you would just end up with a sheet of cells."

The researchers implanted the bioactive scaffold under the skin of mice with severe combined immunodeficiency, removing it after 35 days. Tests then showed that the cells had formed new cartilage.

In Tissue Engineering, Vats and her colleagues wrote, "In our experiments, the human ESCs were separated from [the chondrocytes] by a well insert membrane, so the factors that elicited this effect must have been produced by the chondrocytes and be diffusible through the insert membrane. These results support the hypothesis that differentiation of pluripotent ESCs requires the presence of differentiation factors, which may be provided from the tissue that they are being instructed to differentiate toward."

The group now is embarking on animal trials of the technique and hopes to begin clinical trials within five to 10 years.