Scientists use skin cells to create artificial sperm and eggs
Scientists use skin cells to create artificial sperm and
eggs
Early-stage sex cells research in Cambridge has potential
to help people with fertility problems
Ian Sample, science editor
Wednesday 24 December 2014 12.00 EST
Scientists have made primitive forms of artificial sperm
and eggs in a medical feat that could transform the understanding of
age-related diseases and fertility problems.
Researchers in Cambridge made the early-stage sex cells
by culturing human embryonic stem cells under carefully-controlled conditions
for a week.
They followed the success by showing that the same
procedure can convert adult skin tissue into precursors for sperm and eggs,
raising the prospect of making sex cells that are genetically matched to
patients.
The cells should have the potential to grow into mature
sperm and eggs, though this has never been done in the lab before. The next
step for the researchers will be to inject the cells into mouse ovaries or
testes to see if they fully develop in the animals.
British law prohibits fertility clinics in the UK from
using artificial sperm and eggs to treat infertile couples. But if the law was
revised, skin cells could potentially be taken from patients and turned into
genetically identical sperm or eggs for use in IVF therapies.
Skin cells from a woman could only be used to make eggs
because they lack the Y chromosome. Those from a male might theoretically be
turned into eggs as well as sperm, but Azim Surani, who led the work at the
Gurdon Institute in Cambridge, said that on the basis of current knowledge,
that was unlikely.
“It’s not impossible that we could take these cells on
towards making gametes, but whether we could ever use them is another question
for another time,” Surani told the Guardian.
Researchers have made sperm and eggs from rodent stem
cells before but have struggled do the same with human cells. In 2012, Japanese
scientists created mouse eggs from stem cells and used them to make baby mice.
Three years earlier, scientists at Newcastle University claimed to have made
human sperm from stem cells, but their scientific paper was retracted amid
allegations of plagiarism. In 2002, US researchers produced male and female
mouse pups from male stem cells.
Surani’s team tried a number of different approaches
before hitting on a culture process that turned up to half of the human stem
cells in the dish into precursors of sperm and eggs. Over the five day process,
the scientists added natural chemicals called growth factors to nudge the cells
in the right developmental direction.
“It’s remarkably fast. We can now take any embryonic stem
cell line and once we have them in the proper conditions, we can make these
primordial cells in five to six days,” Surani said. Details of the work, a
collaboration with the Weizmann Institute in Israel, are published in the
journal, Cell.
Through studying the cells, scientists hope to unravel
how sperm and eggs arise and mature into adult sex cells. The ability to make
immature sperm and eggs from patients’ skin means scientists will be able to
compare how they develop differently when they are made from healthy versus
infertile people. “This is really the foundation for future work,” Surani said.
Perhaps more intriguingly, the cells may hold the secrets
for treating certain age-related diseases. As people age they accumulate not
only genetic mutations, but other changes to their DNA. These epigenetic
changes can be caused by smoking, exposure to chemicals in the environment, or
diet and other lifestyle factors. But the cells that form sperm and eggs are
wiped clean of their epigenetic changes early on. “This could tell us how to
erase these epigenetic mutations. Epigenetics is used to regulate gene
expression, but in age-related diseases, these changes can be aberrant and
misregulate genes,” Surani said.
Allan Pacey, senior lecturer in andrology at the
University of Sheffield, said that Surani’s cells could have other uses too.
When men are given chemotherapy it makes them infertile. Dishes of human sperm
cells could be used to understand why, and to screen new anti-cancer drugs that
are not so damaging to sperm.
In the course of their work, Surani’s team discovered
that a specific gene, named SOX17, was crucial for turning human stem cells
into early-stage sperm and eggs. The finding was a surprise, because in mice
the equivalent gene does not play any role. The implications are wide-ranging.
“Mice are the key model we use to study mammalian development and we
extrapolate from mice to humans,” said Surani. “This work tells us that the
extrapolation can be unreliable. I’m not saying that all work in mice doesn’t
apply in humans, but there are fundamental differences we need to be wary of,”
he said.
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