A LITTLE tinkering may be all normal human cells need to make them grow
limitless supplies of tissue for transplant, studies suggest. The work
challenges the widely held belief that most mammalian cells are intrinsically
mortal.
While bacterial cells can replicate forever, human cells can only divide a
limited number of times without an enzyme called telomerase, which repairs the
ends of chromosomes. Even with telomerase, many cells grind to a halt after a
few dozen divisions. Biologists thought that this 鈥渞eplicative senescence鈥� was a
fundamental property programmed into each cell.
Apart from cancer cells, the only human cells supposed to be capable of
dividing indefinitely were primitive cells called stem cells. But while stem
cells鈥� potential for growing replacement tissues has generated much excitement,
in adults these cells are rare and hard to isolate.
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Now cell biologist Woodring Wright of the University of Texas Southwestern
Medical Center in Dallas and his colleagues have shown that if you engineer
human skin cells called keratinocytes to express telomerase, they can continue
to grow.
In normal growth media, even keratinocytes with telomerase divide only a few
dozen times. But change the engineered cells鈥� diet and they go on dividing,
Wright鈥檚 team will report next month in the journal Genes &
Development. What鈥檚 more, the cells make the leap to immortality without
acquiring any of the undesirable characteristics of cancer cells, such as
uncontrollable growth.
鈥淭his doesn鈥檛 mean that growing every cell will be easy. But it suggests that
if we can stumble across the right growth conditions, off you go,鈥� says Wright.
鈥淭here may be no fundamental obstacles to tissue engineering with normal human
肠别濒濒蝉.鈥�
Studies of rat cells by two teams at University College London support
Wright鈥檚 conclusions. Unlike most human cells, rat cells normally express the
telomerase gene. Despite this, rat cells still divide only a few dozen times in
culture.
The UCL teams have shown that some rat cells stop dividing in the lab only
because of the mixture they are normally grown in. Given a more optimal brew,
the cells managed dozens or even hundreds of divisions without signs of ill
health, the researchers will report in Science.
It is possible any cell expressing telomerase can proliferate indefinitely in
an appropriate culture, they conclude. 鈥淭he cells have a much greater capacity
to grow than anyone imagined,鈥� says one of the researchers, Dean Tang, who has
since moved to the University of Texas in Smithville.
However, transplanting human cells engineered to express telomerase into
people isn鈥檛 ideal, because such cells could more easily become cancerous. But
it might be possible to engineer cells so that the telomerase gene is only
turned on while the cells are growing in culture, outside the body.