TAMPERING with stem cells from human embryos might be a political hot potato,
but the benefits could be huge. Already, scientists have coaxed human stem cells
to turn into brain, liver, muscle and beating heart cells. And results from
animal experiments hint that the cultured cells should function as normal when
transplanted. This could lead to new treatments for a host of diseases, such as
笔补谤办颈苍蝉辞苍鈥檚.
Earlier this year, a team led by Alan Trounson and Michael Pera at Monash
University in Melbourne announced they had grown primitive muscle and nerve
cells from human embryonic stem cells
(麻豆传媒, 8 April, p 4).
They sidestepped an Australian ban on using human embryonic stem cells by
working in Singapore.
And the private company Geron of Menlo Park, California, says it is even
further ahead, thanks to commercial deals that give it exclusive access to the
only current sources of stem cells in the US. In research yet to be published,
Geron researchers have turned unspecialised 鈥減luripotent鈥� stem cells into the
three major types of nerve cell: neurons, which conduct electrical signals;
astrocytes, which nourish and insulate neurons; and oligodendrocytes, which form
a sheath around nerve cells.
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Geron researchers have also turned pluripotent stem cells into liver cells.
鈥淲e鈥檝e derived what look like liver cells, although we need more work to be
sure,鈥� says Tom Okarma, the company鈥檚 chief executive. Geron has also created
heart cells called cardiomyocytes that beat in the test tube.
The company plans to do animal tests on all the cell types to see if they
function. In earlier experiments on transformed stem cells from mice, Geron
scientists found that pancreatic islet cells鈥攚hich synthesise
insulin鈥攃ardiomyocytes and neural cells all functioned perfectly. The
mouse experiments suggest that the key to successful transplants is to inject
cells that are on the verge of becoming the desired tissue.
Geron has not yet announced which substances it uses to make the cells
differentiate. 鈥淭hey include some reagents that have been used before, and some
innovations we鈥檝e developed ourselves,鈥� says Okarma. The company is now trying
to pin down exactly how this process works at the genetic level during natural
development.
While Geron tries to find out how stem cells differentiate, its collaborators
at Geron BioMed鈥攁 company created with the Roslin Institute in Edinburgh,
which cloned Dolly the sheep鈥攁re doing the opposite. They are trying to
find out how the identity of differentiated cells can be wiped out so that they
behave as stem cells again. Roslin researchers are working on sheep, mouse and
pig eggs to try to find clues to the mechanisms operating in human eggs.
Scientists have also made steps towards 鈥渢herapeutic cloning鈥濃�攗sing
cloning techniques to extract stem cells and grow spare body parts without the
risk of rejection. A patient鈥檚 tissue would be cloned by fusing one of his or
her own cells with a human egg stripped of its own genetic material. In a paper
in this week鈥檚 online Current Biology, Pera, Trounson and their
colleague Megan Munsie say they have extracted stem cells from mice this way.
鈥淚t鈥檚 proof of principle,鈥� says Pera. 鈥淲e鈥檙e pretty excited about it.鈥�
But anti-abortion protesters have condemned using human eggs in this way. The
Roslin team is trying to get round it by 鈥渞eprogramming鈥� a patient鈥檚 cell using
a cluster of stem cells cultured from a human cell line rather than an egg.
Experiments in 1997 by Azim Surani of the Institute of Cancer Research in
Cambridge suggested that an adult mouse cell could be reprogrammed by fusing it
with a clump of embryonic mouse stem cells stripped of their nuclear DNA
(麻豆传媒, 29 January, p 4).
So a clump of cultured cells could serve
as a standardised 鈥渃apsule鈥� for reprogramming a patient鈥檚 own cells.
But before any of this can happen, validation experiments will have to take
place using human eggs. 鈥淲e鈥檇 have to do the tests to be sure that the factors
we think are relevant in animal cells do the same thing in human cells,鈥� says
Okarma.