Stem
cells found in amniotic fluid can be transformed into a more versatile
state similar to embryonic stem cells, according to a study published
today in the journal Molecular Therapy. Scientists from Imperial College
London and the UCL Institute of Child Health succeeded in reprogramming
amniotic fluid cells without having to introduce extra genes. The
findings raise the possibility that stem cells derived from donated
amniotic fluid could be stored in banks and used for therapies and in
research, providing a viable alternative to the limited embryonic stem
cells currently available.
Amniotic
fluid surrounds and nourishes the fetus in the womb. It can be
extracted through the mother’s abdomen using a needle in a process
called amniocentesis, which is sometimes used to test for genetic
diseases. The fluid contains stem cells that come from the fetus. These
cells have a more limited capacity to develop into different cell types
than stem cells in the embryo.
The
researchers used stem cells from amniotic fluid donated by mothers
undergoing amniocentesis for other purposes during the first trimester
of pregnancy. The cells were grown on a gelatinous protein mixture in
the lab and reprogrammed into a more primitive state by adding a drug
called valproic acid to the culture medium. An extensive set of tests
found that these reprogrammed cells have characteristics very similar to
embryonic stem cells, which are capable of developing into any cell
type in the body—a property known as pluripotency.
Even
after growing in culture for some time, the reprogrammed cells were
able to develop into functioning cells of many different types,
including liver, bone and nerve cells. They also maintained their
pluripotency even after being frozen and rethawed.
The
results suggest that stem cells derived from amniotic fluid could be
used in treatments for a wide range of diseases. Donated cells could be
stored in banks and used in treatments, as well as in disease research
and drug screening. A previous study estimated that cells from 150
donors would provide a match for 38% of the population.
Alternatives
to embryonic stem cells are keenly sought because of ethical concerns
and limited availability of donor embryos. Previous research has shown
that it is possible to make adult cells become pluripotent by
introducing extra genes into the cells, often using viruses. However,
the efficiency of the reprogramming is very low and there is a risk of
problems such as tumours caused by disrupting the DNA. The new study is
the first to induce pluripotency in human cells without using foreign
genetic material. The pluripotent cells derived from amniotic fluid also
showed some traits associated with embryonic stem cells that have not
been found in induced pluripotent stem cells from other sources.
Amniocentesis is associated with a small risk of causing a miscarriage, estimated to be about one in 100.
Dr
Pascale Guillot, from the Department of Surgery and Cancer at Imperial,
said: “Amniotic fluid stem cells are intermediate between embryonic
stem cells and adult stem cells. They have some potential to develop
into different cell types but they are not pluripotent. We’ve shown that
they can revert to being pluripotent just by adding a chemical reagent
that modifies the configuration of the DNA so that genes that are
expressed in the embryo get switched back on.
“These
cells have a wide range of potential applications in treatments and in
research. We are particularly interested in exploring their use in
genetic diseases diagnosed early in life or other diseases such as
cerebral palsy.”
Dr
Paolo De Coppi, from the UCL Institute of Child Health, who jointly led
the study with Dr Guillot, said: “This study confirms that amniotic
fluid is a good source of stem cells. The advantages of generating
pluripotent cells without any genetic manipulation make them more likely
to be used for therapy.
“At
GOSH we have focused on building organs and tissues for the repair of
congenital malformations, which are usually diagnosed during pregnancy.
Finding the way of generating pluripotent cells from the fluid that
surround the fetus in the womb move us one step further in the this
direction”.
The study was funded by the Genesis Research Trust, the Henry Smith Charity and Action Medical Research.
The
children’s charity Action Medical Research are funding the researchers
to explore the therapeutic benefits of transplanting donated placental
stem cells from healthy babies to babies with brittle bone disease.
Dr
Caroline Johnston, Research Evaluation Manager with children’s charity
Action Medical Research said: “These new findings could be a step
forward for treatments of a wide range of diseases that affect babies
and children. We are proud of our history of funding medical
breakthroughs and of our support for these researchers in their move
towards life changing therapies.”
Source: Imperial College London