Tissue engineering becomes clinical reality

Currently, skin remains at the forefront of tissue engineering. But, other tissues, including cartilage and bone, follow closely.

"The development of culture technology expanding keratinocytes from a single cell suspension was established in the 1970s, has huge expansion potential and was rapidly applied to the clinical imperative of treating burn patients - the first being treated in Boston in 1981," says Irene M. Leigh, D.Sc. (Med), professor of cellular and molecular medicine, Centre for Cutaneous Research, Barts and the London, Queen Mary's School of Medicine and Dentistry, University of London. Dr. Leigh spoke at the regional Asian-Australian conference on Dermatology here.

"However," Dr. Leigh says, "tissue engineering as a discipline is very recent, and other products are now where skin was in the 1990s - moving out of the laboratory into more extensive clinical testing."

Perhaps the most tantalizing example of the trend involves stem cell research.

"Growing skin expands adult som-atic stem cells within the basal layer of the skin, but earlier progenitors may also be a source for tissue regeneration," Dr. Leigh says.

"Mesenchymal stem cells can be differentiated into bone- and cartilage-producing cells, but not into epithelial cells. However, there is some evidence that bone marrow stem cells can be integrated into epithelial tissues in kidney and liver repair. So, if bone marrow stem cells can be integrated into skin they might be able to generate skin grafts. We need to know more about how it happens before one could think of it being applied in a tissue engineering situation," she says.

Further down the road, pluripotential hair follicle bulge stem cells might provide a solution for hair replacement, but not for 10 to 20 years, according to Dr. Leigh.

"We know that hair follicle stem cells can produce all the cells of a hair follicle and that they need to be in the right niche with the right connective tissue to do that (Barrandon et al. J Investig Dermatol Symp Proc. June 2003;8(1):28-38). We need to understand the key biochemical regulators of this process before we can attempt to reproduce in the lab," she says.

Burn treatment Burn treatment is more pressing. In this area, Dr. Leigh recommends early excision and grafting when feasible, pretreatment of wounds with a dermal substitute, and application of cultured autologous cells as early as possible, preferably using means including carrier membrane/beads, mats of HA, fibrin, fibrinogen and dermis components.

Keratinocyte grafting represents a treatment option for major thermal burns, as well as for problems including chronic leg ulcers and surgical excisions involving tattoos and scars.

Other uses for this technology range from oral mucosal grafts to separation of conjoined twins. But so far, practical considerations have hampered its applications outside laboratory, Dr. Leigh says.

"Most of the companies providing cultured skin grafts have found difficulty in sustaining the products, as they were too costly. Treating individual burn patients might require $500,000. That's why in the United Kingdom we are taking a National Health Service approach - a small number of manufacturing labs will be approved and registered as part of the health service, as is the case with blood transfusions, organ transplants and cadaver skin banks. Autologous keratinocytes will be provided only for life-threatening situations, as such treatments are very costly and labor-intensive," she says.