Scientists grow human organs for transplant inside pigs

Scientists in the United States are trying to grow human
organs inside pigs.
They have injected human stem cells into pig embryos to
produce human-pig embryos known as chimeras.
The embryos are part of research aimed at overcoming the
worldwide shortage of transplant organs.
The team from University of California, Davis says they
should look and behave like normal pigs except that one
organ will be composed of human cells.
The human-pig chimeric embryos are being allowed to
develop in the sows for 28 days before the pregnancies are
terminated and the tissue removed for analysis.
The BBC’s Panorama was given exclusive access to the
research for Medicine’s Big Breakthrough: Editing Your
Genes.
Creating a chimera
Creating the chimeric embryos takes two stages. First, a
technique known as CRISPR gene editing is used to remove
DNA from a newly fertilised pig embryo that would enable
the resulting foetus to grow a pancreas.
This creates a genetic “niche” or void. Then, human induced
pluripotent (iPS) stem cells are injected into the embryo. The
iPS cells were derived from adult cells and “dialled back” to
become stem cells capable of developing into any tissue in
the body.
The team at UC Davis hopes the human stem cells will take
advantage of the genetic niche in the pig embryo and the
resulting foetus will grow a human pancreas.
Pablo Ross, a reproductive biologist who is leading the
research told me: “Our hope is that this pig embryo will
develop normally but the pancreas will be made almost
exclusively out of human cells and could be compatible with
a patient for transplantation.”
But the work is controversial. Last year, the main US medical
research agency, the National Institutes of Health, imposed
a moratorium on funding such experiments.
The main concern is that the human cells might migrate to
the developing pig’s brain and make it, in some way, more
human.
Pablo Ross says this is unlikely but is a key reason why the
research is proceeding with such caution: “We think there is
very low potential for a human brain to grow, but this is
something we will be investigating.”
Biological incubator
His team has previously injected human stem cells into pig
embryos but without first creating the genetic niche. Prof
Ross said although they later found human cells in several
parts of the developing foetus, they “struggled to compete”
with the pig cells. By deleting a key gene involved in the
creation of the pig pancreas, they hope the human cells will
have more success creating a human-like pancreas.
Other teams in the United States have created human-pig
chimeric embryos but none has allowed the foetuses to be
born.
Walter Low, professor in the department of neurosurgery,
University of Minnesota, said pigs were an ideal “biological
incubator” for growing human organs, and could potentially
be used to create not just a pancreas but hearts, livers,
kidneys, lungs and corneas.
He said if the iPS cells were taken from a patient needing a
transplant then these could be injected in a pig embryo
which had the key genes deleted for creating the required
organ, such as the liver: “The organ would be an exact
genetic copy of your liver but a much younger and healthier
version and you would not need to take immunosuppressive
drugs which carry side-effects.”
But Prof Low stressed that the research, using another form
of gene editing called TALENs, was still at the preliminary
stages, trying to identify the target genes which must be
removed in order to prevent the pig from developing a
particular organ.
His team is also trying to create dopamine-producing human
neurons from chimeric embryos to treat patients with
Parkinson’s disease.
These embryos have been allowed to develop for up to 62
days – the normal gestation period is around 114 days.
Like the team in California, Prof Low said they were
monitoring the effects on the pig brain: “With every organ
we will look at what’s happening in the brain and if we find
that it’s too human like, then we won’t let those foetuses be
born”.
Animal viruses
Gene editing has revitalised research into
xenotransplantation, and the concept of using animal organs
for humans.
In the mid-90s there were hopes that genetically modified
pigs might provide an endless supply of organs for patients,
and that cross-species transplants were not far off.
But clinical trials stalled because of fears that humans might
be infected with animal viruses.
Last year, a team at Harvard Medical School used CRISPR
gene editing to remove more than 60 copies of a pig
retrovirus.
Prof George Church, who led the research, told me: “It
opens up the possibility of not just transplantation from pigs
to humans but the whole idea that a pig organ is perfectible.
“Gene editing could ensure the organs are very clean,
available on demand and healthy, so they could be superior
to human donor organs.”
Animal suffering
But organisations campaigning for an end to factory farming
are dismayed at the thought of organ farms.
Peter Stevenson, from Compassion in World Farming, told
me: “I’m nervous about opening up a new source of animal
suffering. Let’s first get many more people to donate organs.
If there is still a shortage after that, we can consider using
pigs, but on the basis that we eat less meat so that there is
no overall increase in the number of pigs being used for
human purposes.”
In Greek mythology, chimeras were fire-breathing monsters
composed of several animals – part lion, goat and snake. The
scientific teams believe human-pig chimeras should look
and behave like normal pigs except that one organ will be
composed of human cells.
Scott Fahrenkrug, whose Minnesota-based company
Recombinetics is teaming up on the chimera research with
Prof Low, told me: “Perhaps the term chimera is going to
take on a new meaning and it will be one that’s much more
affectionate: chimeras will be seen to be what they are
which is a saviour, given that they will provide, life-saving,
sustaining organs for our patients.”
Seven thousand people in the UK are on the transplant
waiting list and hundreds die each year before a donor can
be found.
Panorama – Medicine’s Big Breakthrough: Editing Your
Genes will be shown on BBC1 at 20.30 BST on Monday 6
June 2016 and will be available afterwards on BBC
iPlayer

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