Medical Research Council (MRC) scientists have for the first
time managed to turn stem cells into the specialised cells that go
on to form spinal cord, muscle and bone tissue in the growing
embryo.
Their discovery could lead to a new way of studying degenerative
conditions such as spinal muscular atrophy, which affects the nerve
cells in the spinal column, and may pave the way for future
treatments for this and other neuromuscular conditions.
During normal embryo development the spinal cord, muscle and
skeleton all form from a group of cells called NMPs
(neuro-mesodermal progenitors). This process is driven by a series
of carefully timed chemical signals, which instruct NMPs to turn
into the different cell types in the growing embryo.
By carefully studying and then mimicking this process in a petri
dish, researchers at the MRC National Institute for Medical
Research (NIMR; now part of the Francis Crick
Institute) and the MRC Centre for Regenerative Medicine, at
the University of Edinburgh, were able to coax mouse and human
embryonic stem cells into becoming NMPs and then spinal cord
cells.
Dr James Briscoe of NIMR said: "There have been some great
advances in the field of stem cell research in recent years, with
scientists being able to grow liver, heart and even some brain
tissue in the lab. The spinal cord, however, has remained elusive
because the NMP cells have largely been overlooked - even though
they were first discovered more than 100 years ago.
"The real breakthrough for us was realising that we had to coax
the stem cells into this intermediate 'stepping stone' cell type
before turning them into spinal cord and muscle cells. We can't yet
produce the tissues themselves, but this a really big step. It's
like being able to make the bricks and raw materials but not yet
build the house."
Researchers have previously been able to grow some types of
nerve, muscle and bone cells in the lab by converting them directly
from stem cells. But this is the first time the intermediate NMP
cell type, which acts like a 'stepping stone', has been created
from stem cells. The advantage provided by guiding cells through
the routes used in normal development is that the resulting cells
may bear closer resemblance to those that occur naturally in the
body. This may help any future therapy utilising these cells by
providing positional cues to allow them to better integrate with
the surrounding tissue.
In the near-term being able to grow NMP cells in the lab will
allow researchers to learn more about normal human development in a
part of the embryo that is otherwise difficult to study. In future
the method could also be refined to allow scientists to grow tissue
from patients with diseases that affect the spinal cord, muscles,
or the motor neurones that connect muscles to the brain and spinal
cord. This would provide a powerful new tool to study in a dish how
these diseases progress and take hold in the body.
Professor Val Wilson of the MRC Centre for Regenerative Medicine
added: "NMPs are important because they're the source of the spinal
cord and most of the bones and muscles in our body.
"But they have been like Cinderella cells. Although recognised
for more than a century in the embryo, they've tended to be ignored
by scientists trying to make these cell types in a dish. We hope
this work will bring them out of obscurity and highlight their
importance."
The paper, In vitro generation of neuromesodermal progenitors reveals distinct
roles for Wnt signalling in the specification of spinal cord and
paraxial mesoderm identity, is published in PLOS
Biology.