A seminar entitled "Tissue Engineering - the New Frontier of Medical Science" was held at the National University of Ireland, Galway, on November 5th. It was brought to my attention by Clive Lee, Professor of Anatomy at the Royal College of Surgeons in Ireland and a researcher in this exciting new field at the Centre for Bio-Engineering at TCD, writes Dr William Revie.
Tissue engineering has been under intense research and development for the last 10 years. It applies the principles of the life sciences and engineering to develop biological substitutes that restore, maintain or improve human tissue function. The ability to engineer new tissue that can replace tissue lost to injury, disease, ageing or genetic abnormality is an exciting development with past vast potential.
Some few organs, such as the hip, can be replaced by artificial mechanical analogues when they fail, but in most cases organ transplantation is the only option. If you were faced with impending liver failure, for instance, you would have no choice but to have a transplant. Organ transplantation is a great medical development and has saved or extended the lives of very many people, but there are risks. You are placed on a waiting list pending the availability of a suitable donor organ. There is a serious shortage of donor organs and you may die before a suitable organ becomes available. When an organ does become available, complex surgery is required to effect the transplantation and surgery always carries some risk.
More seriously, your body will reject the donor organ unless your immune system is artificially suppressed, and this suppression will be a life-long requirement. Despite this you may still reject the transplanted organ. Finally, even with successful surgery and effective immune suppression, the new organ may fail to start-up and function properly.
Now consider the tissue engineering approach, which is basically to construct a new organ starting with a small piece of your own tissue. A small amount of your own tissue - say your liver - is taken. The piece is small enough not to compromise the function of the donor site. Some cells are removed, and the cell population is expanded and reimplanted in your body using a carrier material, where it generates a whole new organ. This organ is made from your own cells and will not be rejected. Most tissue-engineered constructs have at least two important components: a group of cells and a material scaffold on which they can grow. The cells divide and produce new tissue. The scaffold provides the mechanical stability of the construct in the short term and guides the 3-D organisation of the developing tissue. The scaffold is biodegradable and gradually disappears over time, leaving the cells embedded in their own extra cellular matrix. This matrix is made, repaired and remodelled by the cells so that it doesn't degrade with time.
The principles of tissue engineering have been applied to virtually every organ system in the body, including bone, cartilage, tendon, ligament, skin, heart valves, blood vessels, pancreas, gastrointestinal tract, peripheral nerves, spinal cord, teeth and eyes. Engineered skin is currently being used successfully in America. The traditional treatment for limited skin burn or injury is to graft on some new skin obtained from elsewhere on the patient's body. However, in cases of severe injury that is not feasible. Tissue-engineered skin products are now available, prepared from cells extracted from newborn foreskin following circumcision. The engineered skin product does not cause rejection reactions that are clinically detectable. Engineering skin grafts, in addition to curing chronic wounds and skin diseases, could be used to facilitate tattoo removal and to rejuvenate aged skin.
Other exciting developments in tissue engineering include the stimulation of new bone growth, the growth of new heart muscle and the possibility of regenerating entire new limbs. By 2007 it is hoped that doctors treating bone injuries will routinely take a biodegradable matrix from the refrigerator loaded with cells and cellular growth factors. That matrix will grow new bone to replace bone lost due to accidents or bones destroyed by disease. It is hoped that a similar technique can be used to grow new heart muscle and repair damaged tissue following a heart attack. Amphibians can regenerate arms or legs lost to trauma or disease. Unlike mammals, amphibians have a simple immune system. The complex immune system in mammals prevents further generation of cells when normal growth is complete. It may be possible in the future to override this inhibitory system temporarily to allow regeneration of limbs lost to trauma.
Tissue engineering is the main research activity of the Centre for Bio-Engineering at TCD, concentrating on cartilage and bone tissue engineering under the direction of Prof Patrick Prendergast. Vascular graft tissue engineering research is being carried out at the University of Limerick by Dr Tim McGloughlin. Results obtained in research to date have been very exciting and we can expect applications in human clinical medicine to come on-stream within the next five to 10 years.
William Reville is Associate Professor of Biochemistry and Director of Microscopy at UCC