Stem cells – the future: an introduction to iPS cells

one of the most extraordinary scientific
discoveries of this century was made by
dr. turned scientist working in Japan
Shinya Yamanaka had been involved in the
field of stem cells for ten years when
his experiments changed the way we
understand human biology
Shinya Yamanaka is a medical doctor and
a scientist he was interested in finding
a way to treat incurable spinal cord
injury patients I was an austere ik
surgeon so I didn’t do any stem-cell
research at that time it was like 20
years ago but I had many difficult
patients suffering from spinal cord
injuries and there are no treatments to
those patients so that’s why I became
interested in basic research because I
thought by doing basic research one day
I may be able to treat help those
patients shannon yarmulkes desire to
help patients led to a brilliant
experiment this took us to the limits of
our knowledge in fact it took us beyond
them and reveal something really
extraordinary there are two types of
stem cells adulthood tissue stem cells
make cells in their own tissues
blood stem cells make blood muscle stem
cells muscle and so on there is another
type of stem cell the embryonic stem
cell these cells are called pluripotent
because as well as making copies of
themselves they can become any of the
different types of cell that make up the
human body so the point about the adult
tissue stem cells is that these are
dedicated cells to repair and maintain
particular tissue the embryonic stem
cells represent very early stage in
development when there is no muscle or
blood or bone there’s nothing else
really there’s just then development
starts with the early embryo and these
pluripotent founder salts and things
become more and more restricted and
channel that’s how the body is built and
it would be a complete chaos if cell
types could stop turning into one
another Shinya already knew from earlier
experiments and cloning that development
could be reversed that a specialized
cell which scientists call
differentiated can produce embryonic
cells but no one knew how this process
worked to find out sheeni looked for
clues inside the cell I knew that X or
embryonic stem cells have factors that
can convert skin cells back to embryo
embryonic state so that’s why we decided
to search for such factors scientists
had no idea what these factors were or
how many would be needed Shinya went
back to basics examining the biology
that gives cells their individual
identities we already knew that each
cell in our body contains something that
determines the what sort of tissue the
cell becomes
it’s so identity
these are the genes in the nucleus the
nucleus in each of ourselves contains 23
pairs of chromosomes made up of long
strands of DNA this is divided into
sections or genes that direct the cell
to make particular proteins these
proteins which scientists sometimes call
factors of what gives us cells their
different identities all of our cells
contain the same genes but in a skin
cell only the genes that make skin
proteins are turned on the active genes
are always in the unwound open areas of
the chromosome all the other genes that
would make a liver a heart or an
embryonic cell are turned off they are
tightly wrapped up and locked away the
remarkable thing that Shinya Yamanaka
did was to question whether a cell had
to stay differentiated might it be
possible to make an already specialized
cell turn back into an embryonic stem
cell in the laboratory he wondered if
the same proteins that keep embryonic
stem cells pluripotent might be able to
reprogram the specialized identity of a
differentiated cell he started with a
list of over 100 Possible’s
he didn’t know if they operated alone or
in combination which would mean over a
million possible variations using an
off-the-shelf computer program Shinya
Yamanaka was able to distinguish the 24
most likely candidates it took years of
work the next step was to narrow down
factors from 24 factors into whatever
required and we found that 4 out of the
24 factors was essential
he took a combination of 4 factors that
normally only act together in the
embryonic stem cell and inserted them
into a skin cell in a process we don’t
fully understand the chromosomes began
to unwind
Sheena’s factors could now attach to the
genes which make embryonic stem cell
proteins the proteins called opt for
socks to klf4 and Semak overwhelmed the
competing message from the skin genes
fooling the salient is thinking it’s in
an embryonic environment
you
as these reprogrammed cells replicate
they become more and more like embryonic
stem cells until eventually they are
indistinguishable from this state it can
now be used to produce any cell in the
body
what I discovered was that we can
convert skin cells back to embryonic
state so we can make stem cells from
skin cells all we have to do is to add
three or four factors into skin cells
that’s all we need from ES cells and we
rock stem cells we can make all the
cells that exist in the body however we
have to destroy embryos in order to
generate a year cells but with our
technology we don’t have to use embryos
anymore we can make ES like stem cells
directory1 from skin cells Shinya
Yamanaka had made a new type of
pluripotent cell called induced
pluripotent stem cells or iPS cells he
first made his discovery studying mice
and quickly showed it also worked for
human cells this was an extraordinary
discovery
Shinya Yamanaka had proven he could turn
a skin cell backwards in time and then
forwards into any other cell in fact it
didn’t just work with skin he could turn
any differentiated cell into an IPS cell
this generated headline news and
astonished scientists all over the world
my reaction was first of all that this
was one of the most profound scientific
developments in our lifetime it
completely turned upside down
everything we’d been taught about
development so we had always been taught
that development was irreversible
everything was a one-way street but in
fact that’s not true
so our notions about development we’re
clearly wrong it isn’t so fixed as we
thought it was it means we have to be
more open in our thinking to what is
biologically possible only Shinya
Yamanaka imagined that it might be
possible to reprogram and differentiate
itself on just a handful of protocols
other scientists were quickly able to
reproduce genius findings the first step
is to remove the meeting we used to
culture our skin cells now we are adding
a new medium containing the
reprogramming factors in a couple of
weeks we shall have some IPS cells in
this dish
so as a result of infecting the skin
cells what you have after a few days is
this nice colonies of cells see here two
clear examples so they are Vann ESL
mythology but now we also know that
there ever quired is in Viana stem cell
status the way is now wide open to stem
cell medicine induced pluripotent stem
cells or iPS cells are a whole new kind
of cell they can provide better ways of
tackling disease and potentially
regenerating the body one of the major
differences between IPS cells and
embryonic stem cells is that IPS cells
can be generated from individual
patients that means they are genetically
identical to the individual patient and
that means if we generate for example
cells for transplantation from IPS cells
they will not be rejected
they will not be recognized by the
patient’s immune system
here we see for the first time a
prospective to derive specialized cells
for example from the patient’s skin and
to mend these cells into brain cells
into insulin producing cells or into
heart cells which can then be used to
supply this individual patient without
the risk of transplant rejection the way
reprogramming works to make IPS cells is
still mysterious although it’s
technically easy it doesn’t always work
completely and can produce cells with
unexpected changes in their genes
scientists are now investigating how to
produce perfect IPS cells that could be
safe to use for treating patients and
although IPS cells provide a way of
making pluripotent cells without using
human embryos which relieves an
important ethical concern they
themselves have raised entirely new
issues I wanted to avoid the usage of
human embryos so uh I think we have
succeeded that goal but as soon as we
succeeded I realized that we have
generated new ESCO issues this was
something no-one had predicted IPS cells
are in theory a belay both sperm and
eggs so they could one day be used to
produce an embryo which could be
implanted and carry to term
so one day it may be biologically
possible to create a human being from a
single piece of skin should we stop this
research it’s too late making IPS cells
is really quite simple for anyone with
basic biological training like all new
technologies we have to weigh up the
potential benefits and potential
drawbacks for instance studying how to
make functional human sperm or eggs from
IPS cells may bring benefits but
infertile couples scientists believe
that the creation of IPS cells means
stem cells have entered a new era
teaching us how to control cell identity
they expect IPS cells to provide us with
new tools to study diseased and normal
cells in the laboratory
meaning that drugs for diseases like
Parkinson’s can be tested on lab grown
human cells they also hope to learn why
human cells die in degenerative diseases
like Alzheimer’s
a key problem in drug development is bad
down individual candidate tracks face
the human system only at a very late
stage of drug development until then
there’s usually up to eight years of
development which has gone into this
individual drug now using human cells at
the very early stage of drug development
will help to identify compounds which do
not work in human cells I think this
this will definitely create new
opportunities to identify new drugs and
speed up the process by which drugs come
through but it will just revolutionize
the approach to studying inherited
disease given a sample of disciple but
only one essence on as I’ve already
filled oh yeah but I mistake what I’ll
be talking to you on what Pelosi’s is
only for doctor
as we thought okay I guess this is the
most important discovery in stem cell
research since embryonic stem cells were
first discovered in 1981 in my personal
opinion it will go down in history as
one of the most amazing discoveries of
all time