IT MIGHT turn out to be the most important cell ever discovered. It’s a stem
cell found in adults that can turn into every single tissue in the body.
Until now, only stem cells from early embryos were thought to be able to do
this. If the finding is confirmed, it will mean cells from your own body could
one day be turned into all sorts of perfectly matched replacement tissues and
even organs.
If so, there would be no need to resort to therapeutic cloning—cloning
people to get matching stem cells from the resulting embryos. Nor would you have
to genetically engineer embryonic stem cells (ESCs) to create a “one cell fits
all” line that doesn’t trigger immune rejection. The discovery of such versatile
adult stem cells will also fan the debate about whether embryonic stem cell
research is justified.
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“The work is very exciting,” says Ihor Lemischka of Princeton University.
“They can differentiate into pretty much everything that an embryonic stem cell
can differentiate into.”
The cells were found in the bone marrow of adults by Catherine Verfaillie at
the University of Minnesota. Extraordinary claims require extraordinary proof,
and though the team has so far published little, a patent application seen by
Â鶹´«Ă˝ shows the team has carried out extensive experiments. These
confirm that the cells—dubbed multipotent adult progenitor cells, or
MAPCs—have the same potential as ESCs. “It’s very dramatic, the kinds of
observations [Verfaillie] is reporting,” says Irving Weissman of Stanford
University. “The findings, if reproducible, are remarkable.”
At least two other labs claim to have found similar cells in mice, and one
biotech company, MorphoGen Pharmaceuticals of San Diego, says it has found them
in skin and muscle as well as human bone marrow. But Verfaillie’s team appears
to be the first to carry out the key experiments needed to back up the claim
that these adult stem cells are as versatile as ESCs.
Verfaillie extracted the MAPCs from the bone marrow of mice, rats and humans
in a series of stages. Cells that don’t carry certain surface markers, or don’t
grow under certain conditions, are gradually eliminated, leaving a population
rich in MAPCs. Verfaillie says her lab has reliably isolated the cells from
about 70 per cent of the 100 or so human volunteers who donated marrow
samples.
The cells seem to grow indefinitely in culture, like ESCs. Some cell lines
have been growing for almost two years and have kept their characteristics, with
no signs of ageing, she says. Given the right conditions, MAPCs can turn into a
myriad of tissue types: muscle, cartilage, bone, liver and different types of
neurons and brain cells. Crucially, using a technique called retroviral marking,
Verfaillie has shown that the descendants of a single cell can turn into all
these different cell types—a key experiment in proving that MAPCs are
truly versatile.
Also, Verfaillie’s group has done the tests that are perhaps the gold
standard in assessing a cell’s plasticity. She placed single MAPCs from humans
and mice into very early mouse embryos, when they are just a ball of cells.
Analyses of mice born after the experiment reveal that a single MAPC can
contribute to all the body’s tissues.
MAPCs have many of the properties of ESCs, but they are not identical. Unlike
ESCs, for example, they do not seem to form cancerous masses if you inject them
into adults. This would obviously be highly desirable if confirmed.
“The data looks very good, it’s very hard to find any flaws,” says Lemischka.
But it still has to be independently confirmed by other groups, he adds.
Meanwhile, there are some fundamental questions that must be answered,
experts say. One is whether MAPCs really form functioning cells. Stem cells that
differentiate may express markers characteristic of many different cell types,
says Freda Miller of McGill University. But simply detecting markers for, say,
neural tissue doesn’t prove that a stem cell really has become a working
neuron.
Verfaillie’s findings also raise questions about the nature of stem cells.
Her team thinks that MAPCs are rare cells present in the bone marrow that can be
fished out through a series of enriching steps. But others think the selection
process actually creates the MAPCs. “I don’t think there is `a cell’ that is
lurking there that can do this. I think that Catherine has found a way to
produce a cell that can behave this way,” says Neil Theise of New York
University Medical School.
Have we found the ultimate stem cell? One that can deliver all the benefits
of embryonic stem cells without having to destroy a potential human life to save
an existing one?
It’s too early to tell, say stem cell researchers. While they are excited
about the potential of an adult stem cell like Verfaillie’s, most insist that
research with embryonic stem cells must continue, because nobody can possibly
know right now which option is better.
And it might be worth it for more than one reason, says Arthur Caplan,
director of the Center for Bioethics at the University of Pennsylvania. Many
scientists—Verfaillie included—are patenting their discoveries,
which could hinder their widespread use. We need to keep all options open, he
says.
But in the US, federally funded researchers have only just been allowed to
work with a limited number of ESC lines. Opponents of such research, who have
long touted adult stem cells as an alternative, are likely to seize upon
Verfaille’s results. As Richard Doerflinger of the US Conference of Catholic
Bishops puts it, the only reason many lawmakers have felt compelled to “cross
the moral line” in backing ESC research is because they believe it’s the only
way to get the full benefits.
Indeed, Erik Parens of bioethics think tank The Hastings Center believes the
discovery could have a negative impact, letting the US dodge the kind of debate
over embryonic research that countries like Britain have had.
The discovery could also affect the cloning laws being drawn up around the
world. While banning reproductive cloning, countries such as Britain have
permitted therapeutic cloning because doctors could use it to obtain ESCs. But
if every human being already has a reservoir of stem cells with similar
potential, should research continue into a technique that could easily be abused
by those eager to create the first cloned babies?
What is a stem cell?
Most cells in the body only get one shot at a career choice. Once a muscle
cell, always a muscle cell. But stem cells are precursor cells that remain
unspecialised, and can go on to form a number of different cell types.
Why all the excitement about them?
In the short term, stem cells could be used to grow new neurons for people
with Parkinson’s or Alzheimer’s, or new insulin-producing cells to treat
diabetes. In the long term, it might be possible to repair damaged spinal cords
or even grow entire replacement organs. If these replacement tissues and organs
were grown from stem cells taken from the patient’s own body, there’d be no
problems with rejection.
So what’s the catch?
Until now, all the stem cells found in adults have had only limited potential
(see main story). An adult stem cell that can form brain cells, for example,
can’t make liver cells. While specific adult stem cells might be fine for some
purposes, only embryonic stem cells taken from the ball of around 60 cells that
forms about six days after an egg is fertilised were thought capable of forming
every type of tissue in the body.
Why bother with adult stem cells then?
There are several problems with embryonic stem cells. Getting them involves
destroying a human embryo, which many people find unacceptable. But even if you
think this is justifiable for treating serious diseases, the only way to get
matching cells for patients would be to clone each individual and take cells
from the embryo—so-called therapeutic cloning. Nobody’s anywhere near
doing this yet, and even if they did, costs are likely to be prohibitive.
Sounds tricky…
That’s not all. In a recent study, a fifth of animals injected with embryonic
stem cells developed untreatable brain tumours. Before they could be used in
people, you’d have to ensure this could never happen.