MAKING cells immortal allows vigorous new tissues to be grown from a person鈥檚 own cells. The technique could improve the quality of a wide range of engineered tissues, from replacement arteries and corneas to skin grafts. But to avoid the risk of cancer, cells will have to be given only a brief taste of the elixir of life.
Nearly 100,000 patients a year in the US need surgery to bypass small arteries, for instance, but have no usable arteries or veins for grafting. It is possible to grow human arteries from umbilical cord cells, but using a patient鈥檚 own cells would prevent immune rejection.
The trouble is that ageing adult cells do not multiply enough to form strong arteries that can withstand the pressure of pumping blood. This is because there are 鈥渇uses鈥� called telomeres on the ends of chromosomes that get shorter each time a cell divides, eventually blocking further division and the formation of new tissues.
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Germ cells and cancer cells produce an enzyme called telomerase that restores telomeres, allowing them to divide indefinitely. Several groups have shown that normal cells can be made immortal too by switching on the telomerase gene. And Laura Niklason and Chris Counter of Duke University in Durham, North Carolina, have now done this with smooth muscle cells taken from a two-year-old鈥檚 aorta. Their team used a retrovirus to add a gene called hTERT, which codes for a key part of telomerase. The modified smooth muscle cells divided more than 100 times, while others died after just 37 generations (EMBO Reports, vol 4, p 633).
A biodegradable tube was then seeded with the souped-up muscle cells, and a nutrient solution pulsed through it to mimic the pumping of blood. The cells formed thick arterial walls, which were then lined with endothelial cells to form complete arteries. It is the first time strong human arteries have been grown using non-neonatal cells. The team is now working with cells from older donors, and other groups are doing similar work with skin and corneal cells.
But implanting cells in which telomerase is permanently switched on would not be safe, as they are one step closer to becoming cancerous. 鈥淭he enzyme is certainly activated in 90 per cent of cancers,鈥� says Counter. 鈥淚t wouldn鈥檛 be wise to have the enzyme in there all the time, particularly in a young person.鈥�
So instead of using retroviruses, the team is now working with adenoviruses. Unlike retroviruses, adenoviruses do not usually integrate their DNA into genomes, which means the hTERT gene would be active only for a few days before being broken down. Whether that is long enough to boost the lifespan of cells remains to be seen, but if it is, the applications seem vast. 鈥淚t will have significance not only in engineering arteries but in other areas as well,鈥� says MIT tissue engineering expert Robert Langer.
For instance, skin cells can already be taken from victims of severe burns and grown in the lab to provide enough skin for grafting. But when Counter鈥檚 team looked at skin cells in such grafts given to children between 5 and 12 years ago, they discovered the cells had dramatically shortened telomeres (Lancet, vol 361, p 1345), which might cause premature ageing. In fact, the telomeres were shorter than those in healthy 80-year-old skin.
This shortening probably occurred when the skin cells were grown outside the body. Temporarily adding the hTERT gene could restore the lengths of telomeres before cells are implanted, says Counter. 鈥淎ny time you are going to take cells out, expand them, and put them back, you may need to reprogram the telomere lengths.鈥�