( applause ) >> Okay, thanks so much, Tom.
And thanks everybody for coming out on a cool November evening.
What I'd like to do today is just talk a little bit about
stem cells and the heart and what that really has
implications for in the way of regenerative medicine.
So we'll start out a little bit by talking about the burden of
heart disease. And from there, we'll go on
to what are stem cells. From there, move on to how our
understanding of cardiac biology has changed, how we can get stem
cells to change in a dish to become heart cells.
And then about cardiac regenerative medicine and the
center here on campus. So we've got a bit to cover
today, but I'd like it to be interactive.
So if you have questions as we go, please feel free to ask
them. I don't know.
Tom, can you turn down the light in front so the screen is a
little brighter, or is that impossible?
Or could I do it, if I was smart enough?
( inaudible ) ( laughter )
While Tom is testing himself here, we'll go on.
So I just want to start because I am a cardiologist here at UW.
That's great. You don't have to turn it down
too low. I am a cardiologist here on
campus, and also have a basic research lab.
The focus of my research is understanding heart disease and
defining new treatments for it. And part of that is in education
and making sure that everyone's aware of really how big a
problem heart disease is. It remains the number one cause
of death in the United States. About 71 million people in the
U.S. live with one or more forms of cardiovascular disease.
It causes about 37% of all deaths in this country.
And it's estimated in direct costs for the U.S. economy
to be about $403.1 billion. So this is a big public health
problem. The majority of the problem here
in this pie graph over here is related to coronary artery
disease. That's the cholesterol building
up in the coronary arteries. That can cause heart attacks, as
well as a range of other cardiovascular diseases here.
But tonight, I'll focus a little bit about coronary artery
disease and what it means to have a heart attack and how cell
therapy may help with that. On this slide, I just give you
some images. These are MRI images that you
may or may not be able to see here.
I'll try and point out. Let's see, does that show up?
That doesn't show up. So there's--
Well, you can't really see it. The walls are squeezing in
in the heart in a normal heart, so I'll just have to describe it
to you. All the walls come in in the
pumping chamber of the heart the left ventricle, equally
and symmetrically to eject the blood.
And what happens with the heart attack is you lose part of that
wall. Here's a heart that had a heart
attack and there's a part of the wall not moving.
Without a pointer, I can't really show you that.
Maybe I'll use this. So this part of the heart, this
black area is the wall. It's should be moving in, and
it's not. And so part of the heart muscle
stops working after a heart attack.
And it becomes scar tissue. So the obvious question is, can
we address that problem with new approaches to repair the injured
heart muscle. So that's where the issue of
stem cells come in. And first, I'll spend a little
time describing what stem cells are and how we understand them.
A simple definition of a stem cell indicates that it has the
ability to divide or self-replicate for, really,
indefinite periods of time, even throughout the lifetime of an
organism. It can differentiate into
various specialized cell types under the right conditions and
it can potentially grow into very mature specialized cells,
such as heart cells and nerve cells.
There are a variety of different types of stem cells.
Embryonic stem cells are one form.
They're isolated from the pre-implantation blastocyst.
That is after the sperm and egg unite to fertilize and form the
zygote. That begins to divide.
It forms the cystic structure called the blastocyst, which is
sort of floating before it implants in the uterus.
And if those inner cell mass cells are isolated from the
blastocyst, they can then be cultured under very special
conditions, originally on a feeder layer of cells that
maintain them as undifferentiated non-specialized
cells that are pluripotent, in that they can give rise to all
the different cell types in the body.
And they can grow indefinitely in culture.
They can also be grown up as single cells into new cultures
of cells. So that's what embryonic stem
cells are. They were first isolated from
the mouse. And mouse embryonic stem cells
were described by Martin and Evans and Kaufman in 1981.
And really set the groundwork for a revolution in biology with
engineered mice models really helping us understand the
function of individual genes by loss of function, knocking out a
gene and seeing what happened to the mouse.
Or gain a function experiments, adding a gene and seeing what
happened to the mouse phenotype and the mouse cells.
So this was a major advance for biology.
And it's created a whole new tool for research.
And even back in 1981, folks thought it would be potentially
useful to have human embryonic stem cells.
But as you can see, it wasn't easy to get the human embryonic
stem cells. Jamie Thomson here was the first
to make a step closer to that when he isolated embryonic stem
cells from non-human primates from the rhesus and marmoset.
And that was published in 1995 and 1996.
But ultimately the interest really ramped up when Jamie
successfully isolated embryonic stem cells from surplus
In Vitro Fertilization embryos in 1998.
That is embryos that were created for couples undergoing
treatment for infertility, and in the process many embryos were
created in a tissue culture dish.
Some of which were implanted in the mother and went on to bear
children. The rest were cryo-preserved
indefinitely, potentially for future use.
But with informed consent, Jamie was able to get these with the
donor's consent, and isolate the embryonic stem cells.
Here, a colony is shown growing on a fetal layer of mass
embryonic fibroblasts, which has been a very powerful tool in
this field. And the latest excitement, as
Tom suggested is related to a new form of stem cell.
This is something called induced pluripotent stem cells.
And really, there have been several labs working hard on
this. Perhaps one of the leading labs
is from Japan. Yamanaka and colleagues started
this work working in mouse and using mouse fibroblasts.
Where they took fibroblasts, which is what we call a
terminally differentiated cell. So we start out in development
as a zygote, a very blank slate cell that then progressively
specializes. And typically, our understanding
of development is as this cell gets more and more specialized,
it can't go backwards and get less specialized with normal
development. And what this work showed is
that if you expressed the appropriate combination of genes
in very specialized mouse fibroblast cells, that you can
reverse their clock and reprogram them so they become
pluripotent. In other words, they can grow
into all different cell types in the body, like embryonic stem
cells. And the most recent proof that
these really are pluripotent cells is that these induced
pluripotent cells were injected into a mouse blastocyst in a
study done by Yamanaka. And in that blastocyst, they
incorporated and they became a chimeric mouse, shown
schematically here after injection into the blastocyst.
So you've got these cells growing into all the different
cell types in the mouse. And then they can even get in
the germ cells and they can do what's called going germline.
So they can form mice from this single induced pluripotent stem
cell. So they are truly pluripotent in
the case of the mouse. And this was sort of a surprise.
People didn't really think it would be that easy to turn the
clock back on cells, to get them to behave like stem cells.
And this is recent work, really starting to come out just last
year. And the most recent paper was
earlier this year. So the field is moving quickly
because just this week we heard about human induced pluripotent
cells that were isolated both by Jamie Thomson here and the
Yamanaka group, where they expressed four genes using a
particular way to transform the cells and get human cells into
these induced pluripotent stem cells that may be important for
regenerative medicine applications.
The figure just shows that in Jamie Thomson's work, they were
able to differentiate these cells into a variety of
different lineages. When they formed teratoma tumor
in mouse cells, they allowed the cells to spontaneously
differentiate into neural-like structures, into cartilage-like
structures, and into gut-like structures.
Just a selection of different tissues that can form.
Again, supporting the idea that these are truly pluripotent stem
cells. And that's not to forget that
there are also stem cells in adults, so-called adult stem
cells, or progenitor cells, are a little more specialized.
Probably the best description of adult stem cells comes from the
blood system in the hematopoietic stem cell.
It's present in our bone marrow, that then can specialize into
what's called a progenitor that can give rise to a variety of
different cell types. If it's a lymphoid progenitor,
it can give rise to lymphocytes, specific blood cells.
If it's a myeloid progenitor, it can give rise to other subsets
of blood cells. And this is sort of the
hierarchy of development of this blood system that's obviously
quite important for us. And this has been, really,
appreciated for a few decades, that the bone marrow contains
stem cells that are able to self-renew.
They undergo what's called asymmetrical division.
So if this cell divides, one cell remains a stem cell, and
the other starts to specialize a little bit.
They are multipotent, but they're not pluripotent.
That means they can differentiate into many cell
types, but they can't differentiate into the full
gamut of cell types present in the human.
And the most rigorous test is you can take a single
hematopoietic stem cell and reconstitute a blood system in
an animal or a human. So really what the hematopoietic
stem cells and more recent technology have given us are
tools to find stem cells in other tissues.
We've known about them in blood for a number of years.
But only really in the last decade or so have we started to
appreciate stem cells in other tissues.
And that's because we've had tools that allow us to identify
those cells. Otherwise, when we do the
standard histology, looking at tissues, the stem cells don't
really stand out as anything special.
And it's only by using antibodies that recognize the
various specialized proteins on those cells, as well as gene
expression studies that we can tell that these are stem cells,
as well as better techniques in microscopy to allow us to look
at the tissues, and better ways to isolate the cells.
And that's important because we'll go on and talk about how
these tools have impacted cardiac biology.
So now we'll start focusing a little bit on the heart and
where I focus most of my effort and energy.
And one of the dogmas of cardiac biology is understanding how the
heart responds to injury. And a common injury is a heart
attack or a myocardial infarction, as I tried to show
you with the movie, which didn't work.
But what happens with the myocardial infarction is a scar
forms. And here is a section through a
heart that's had a myocardial infarction.
And the blue is the area of scar.
All that blue tissue is dead scar tissue.
They are fibroblasts, but there are no red muscle cells.
So this part of the heart won't contract.
So obviously, the larger that is, the bigger the problem is.
It turns out this scar puts stress on the rest of the heart,
causing it to sort of work overtime.
And in the long haul, that causes the heart to do what we
call remodel, get bigger, dilate, and go on to heart
failure. So many forms of heart disease
are associated with loss of functional contracting heart
muscle cells. And so we typically thought that
once you lose the cells, they're gone for good.
And that was the dogma I grew up with in medical school and
largely still the dogma being taught today.
But when people have more recently been looking at things
a little more closely, they found that things don't quite
add up that way. For example, if you're very
meticulous and count the number of heart cells in a rat heart,
there are about 23 million myocytes.
But if you also look at the rate that those myocytes are
undergoing programmed cell death, which is called
apoptosis, about 1.34 million cells die every month.
So if you then take that into consideration and look at 20
months, you'd think there'd really be no heart left.
But it turns out there are some fewer myocytes, but really not
that many fewer. So how are we making up this
difference? How are we making up for the
cells lost via programmed cell death?
Then others have looked for cell division in the heart.
It's been very controversial, hard to find.
But in diseased hearts, they can find some of those myocytes
dividing. So maybe the heart isn't sort of
fixed after you're born, and there is the ability to get new
cells. Another clue along this line
came with work earlier in 2000, where people did sort of
interesting work in heart transplant patients.
Something that modern medicine has created to help patients
that really have no options with a failing heart.
But it's also provided a research tool, and that is, if
you transplant a female heart, females have two X chromosomes,
into a male recipient, males have XY.
And if you look at that female heart later on after it's been
ingrafted, if the patient dies for some reason, and that's how
they got these autopsy samples, you find out that in the female
heart, it should be XX, there are Y chromosomes.
Where did those Y chromosomes come from?
Is there some population of cells getting into that heart
that then are forming heart cells?
So these have been sort of clues out there that maybe the heart
is a little more complicated, and maybe it has some ability to
repair itself. And at the same time, others
have identified adult stem cells in a variety of tissues
including skin, liver, fat, skeletal muscle, the GI tract,
and so forth. So really, the breakthrough
paper came pretty recently, 2003.
We've been studying the heart for a long time.
But just in 2003, really some definitive work was done that
provided evidence that there are stem cells in heart tissue.
So there is a population of adult stem cells, shown here as
these small cells with a rim of green around them.
I'm not sure if you can see that too well.
But that green is identified with an antibody that recognizes
a protein called c-kit, which is particularly present on stem
cells. So these authors did a variety
of other experiments to support the idea that these were stem
cells in the heart. So this really is a fundamental
change in our understanding of cardiac biology and gives us
all sorts of new potential avenues to treat heart disease.
So the good news is that there are cardiac stem or you could
call them progenitor cells identified in the heart.
They're self-renewing. In other words they can grow and
they can grow from a single cell.
They're clonogenic. And they're multipotent.
That is, they can grow into heart muscle cells, but they can
also grow into blood vessel cells.
Having muscle without the blood vessels to supply it
wouldn't be too useful. So these cells can do all that.
So regenerate heart tissue, pretty encouraging.
So the heart, like we also found out in the brain, has primarily
terminally differentiated post-mitotic, so that means very
specialized cells that can't divide anymore.
But it's not simply only those cells.
There's a hidden population of stem cells that have some
ability to repair the heart. And potentially manipulating
those endogenous stem cells holds promise for treatment for
a variety of heart disease. And perhaps some of the most
striking findings were produced by this work in zebrafish where
Mark Keating and colleagues took a zebrafish and they snipped off
the tip of the heart. They just cut it off and threw
it out to see what would happen. And it turns out that a big scar
formed there initially, a blood clot.
But over time, that was replaced, and the heart totally
regenerated in the zebrafish. So zebrafish can totally repair
their heart after an insult like that.
The bad news is we can't. So most of the insults that we
are faced with in adult cardiology, stem cells that are
endogenously present aren't able to take care of it, or we
wouldn't be seeing it clinically.
Why is that? It may be that adult stem cells
become dysfunctional with aging. It could be in diseases like
heart failure, the bone marrow-derived stem cells aren't
working so well. And interestingly, many of the
risk factors for atherosclerosis, in other words,
a cholesterol build-up in the arteries are inversely
correlated with the levels of circulating stem cells.
In other words, if your cholesterol is high, and your
bad cholesterol is particularly high, it knocks back the stem
cells in the circulation. It's sort of a potentially a
one-two punch. So it's nice to know we have
stem cells in our hearts, but the way they are, they're really
not taking care of many of the insults that we're faced with.
So how can we get around that and treat that?
And I think that's where the idea of harnessing the power of
some of these stem cells and the tools of regenerative medicine
will be helpful. Let me just talk about whether
or not these stem cells can actually form heart muscle and
some of the work we've done in our lab.
And that work has looked at the differentiation or
specialization of embryonic stem cells into cardio-myocytes,
using a system where we take the undifferentiated cells and
remove them from the specialized conditions that maintain them
undifferentiated, form clumps of cells in suspension called
embryoid bodies and then plate them down, and they
spontaneously differentiate. We can then plate them on our
little cover slips and look in there.
And we can see contracting cells.
I don't know if you can see that too well.
But there are cells spontaneously contracting.
They give us a not-too-subtle clue that heart cells have
developed. They develop in sort of a random
pattern. This embryoid body formation
doesn't recapitulate formation of an embryo.
Rather, it's a spontaneous process, and some of the
embryoid bodies have these beating areas and some don't.
So we've then gone on to study those using the tools--
( inaudible ) I will do that.
It's not important on this slide.
( inaudible ) I will do that on another slide.
I can read it on my computer screen.
( laughter ) ( inaudible )
Tom would have to do that, because that's again, beyond me.
But maybe he could. ( inaudible )
No, I'll fill in blanks where the red shows up.
But on this slide, don't worry about it.
So what this shows is a schematic diagram where we can
take an electro physiologic apparatus, so an amplifier, and
put an electrode, a micro-electrode, into the cells,
and then measure their electrical activity.
And why might we want to do that?
One of the hallmarks of different types of heart cells
is their electrical signature. Our heart is an electrical
organ. The electrical wave is what
triggers the contraction. So different parts of the heart
have different electrical, what we call action potentials.
So the pacemaker region of the heart, called the sinoatrial
node, sort of has this slow upstroke action potential and
this slow what we call depolarization before it.
But that's quite different than action potentials in the atrium,
the upper chambers of the heart, and the ventricles, the lower
chambers of the heart, which have a much longer plateau
phase. So the four chambers of our
hearts have different types of action potentials.
And that's sort of a nice signature, because it's made up
of the opening, closing and activity of really, dozens, if
not a hundred different electrical ion channels and
transporters. It gives us sort of a
fingerprint of the cell type. And so when we took our
electrode and measured some of these action potentials, or
electrical activity from the embryonic stem cells, we see
that there are a variety of different electrical signals.
There are nodal-like action potentials, suggesting that
nodal-type cardio-myocytes can develop from the human embryonic
stem cells. There are more atrial-like
action potentials, more ventricular-like.
So this is just a general proof of principle that the embryonic
stem cells can form all different types of
cardio-myocytes, which may be useful for different
applications. If you've got a problem with a
ventricle, you'd like to put ventricle cells in there.
If you need a biopacemaker, you might want to think about more
nodal-like cells, for example. Another reason that this might
be important to have these stem cells beating in a dish is
something to do with cardiac drug safety.
Now I have to get you a little more into cardiology.
This is a schematic of an electrocardiogram, and one QRS
complex, which is essentially one heart beat.
And it turns out that from the beginning of the ventricular
activity to the end, which is called the QT interval, depends
on how long the electrical action potential is in the
ventricular muscle. So a longer QT means a longer
action potential. And so we can measure an action
potential in these heart cells. And we can see if a drug makes
that action potential longer. So why am I telling you all
this? It turns out that it's
important, because there are certain potentially lethal heart
rhythms that can be induced by certain drugs.
Not as part of their planned effect, but as sort of a bad
side effect. And this is an example of a
patient actually admitted to UW Hospital, now more than a decade
ago, who came in and was taking an antihistamine called
Hismanal, and had fainted in church.
And she got brought into the ICU, and they monitored her here
with an electrocardiogram. Also put in an intra-arterial
line so they could measure her blood pressure here.
You can see the electrical activity of the heart here.
And a long QT interval is here, which is a sign that the action
potential is long. And what happens is a bad heart
rhythm here that's called Torsades de Pointes.
It goes very fast and you can see the blood pressure goes down
to nothing. So if this wouldn't have
spontaneously broken, this would have been a lethal event, if it
didn't happen in the hospital. And that ultimately, as well as
other studies, led to the withdrawal of this drug from the
market. It's also led to the withdrawal
of several other drugs, and is now screened for.
With all new drugs coming through development, they're
screened for this potential side effect.
But there aren't great models to screen for that.
So potentially using a cell like these embryonic
stem cell-derived cardio-myocytes may provide
a useful tool to help with drug safety, as well as other aspects
of drug development. So now let's talk a little bit
about cardiac regenerative medicine and where we are right
now with that. So regenerative medicine, I
think is an extremely exciting area.
It's really largely new concepts.
And it's rapidly growing. It explores, not only the use of
stem cells and their derivatives to repair damaged tissues, but
also looks at the ability to harness, for example, the body's
own reparative properties using small molecules, for example, to
turn on endogenous stem cells or to alter the ability of the body
to repair itself. So it's a broad area that
encompasses a lot of different approaches.
But if we're going to think about cell therapy, we have to
really take our time and think about the various steps to get
from the research lab to patients.
And the first step, really, is to get a well characterized cell
population. And develop, if we're going to
do tissue engineering, making pieces of tissue that will then
implant into a patient. We have to really develop the
appropriate materials to do that.
And then test their properties In Vitro, that is in a cell
culture dish. And then use them in animal
models of disease, understanding how best to put them in the
animal models to deliver them, understanding how to prevent the
animals from rejecting them as foreign substances.
Ultimately, we'd like to see in the animal models that they're
effective and that they can ingraft, integrate into the host
tissue. Improve the function of the host
tissue and cause the disease to get better.
But at the same time, equally and maybe more important, they
have to be safe. We don't want to bring along
infectious agents. We don't want to have any tumors
formed. And we don't want any other
potential problems, such as arrhythmias to come up.
And then, ultimately these will get into human trials.
So there's a bit of work to do before we get to patients with
most of these cell-based applications.
For cardiac cell repair, and many of the most prevalent forms
of heart disease, are associated with a loss of function
cardio-myocytes. So it is appealing to think
about getting new cells in there.
Whether it's coronary artery disease with a myocardial
infarction, causing the loss of a big piece of the heart, heart
failure with loss of functioning heart cells, certain arrhythmias
are due do the loss of heart muscle.
And maybe engineering new valves could take advantage of new cell
therapies and tissue engineering.
A variety of different cell sources have been considered for
this. And many have already been
tested, whether it's stem cells from the blood, so-called
endothelial precursor cells, mesenchymal stem cells from
skeletal muscle, from fat. And we've talked a little bit
about embryonic stem cells, and also stem cells even from the
heart itself. It's also important to think
about your source of donor cells, whether they come from
self, or whether they come from non-self sources.
So we call that autologous if it's from self.
So if you give some of your own bone marrow and they purify that
to transplant into a heart. Or endothelial precursor cells
are isolated from your blood, skeletal myoblasts from your
muscle biopsy. Maybe what's on the forefront is
the new induced pluripotent cells from a skin sample.
Or cells isolated from your heart or cord blood cells.
But maybe allogeneic cells will be a potentially important
source. Right now, the embryonic stem
cells represent an allogeneic source.
Mesenchymal stem cells are another allogeneic source, or
baby cord blood from other folks would be allogeneic or non-self
source of cells. So again, probably hard to see
here, and I'm sorry about that. This is a slide that really got
us going down this road quickly. This is an experiment done,
really, in early 2000 and 2001, by Peiro Anversa's lab and Don
Orlic's lab, where they did sort of an interesting experiment.
They took blood stem cells. So they isolated stem cells out
of the bone marrow, isolated the stem cell population there.
And it was from a mouse that expresses a protein called green
fluorescent protein. So all those cells are GFP
positive, which means they're green under the appropriate
illumination. They transplanted them to a
mouse that they tied off the coronary artery, so that mouse
had a heart attack. Then they saw what those cells
did. And here you barely can see,
there are a bunch of green cells.
But in the same range of tissue, there's also staining for a
cardiac protein called myosin, suggesting those green cells, or
those transplanted cells became heart tissue in the area of
injury and are regrowing heart muscle.
So that got everybody pretty excited to think that you could
take bone marrow-derived stem cells and regenerate heart
muscle. So that really got this field
jump started. But it hasn't been without some
controversy. A couple of other prominent labs
have said that bone marrow stem cells do not regenerate
infarcted myocardium. And this was, again, published
in a fairly prominent journal, Nature, three years later.
And so this has been an area of some controversy as to what the
cells do. We, in our lab, used another
cell population. And that is mouse embryonic stem
cells, and transplanting them into a mouse heart model.
And again, green cells have a reporter protein to tell us
where the cells came from. And hard to see here, but this
is an area of regenerated heart muscle.
And the red is an antibody to what's called smooth muscle
actin. So these are a couple of blood
vessels you may be able to see. And this is regenerated blood
vessel and heart tissue here. We think that transplanting
embryonic stem cells can help the heart.
And what we, and many other labs, have found is that
transplanting these stem cells has a significant functional
impact on the heart, in that if you look, these are what are
called M-mode echocardiograms. What you see is after a heart
attack, this is a particular measurement of how big the
chamber is of the mouse heart. It's called the Left Ventricular
End Diastolic dimension for the aficionados.
It gets bigger after a heart attack.
That is, the heart dilates after a heart attack, after
myocardial infarction. And transplanting the stem cells
blunt that, what we call remodeling of the heart.
So the heart doesn't dilate as much after the heart attack.
Likewise, the contraction of the heart, here shown as fractional
shortening, gets much less, because you're losing
functioning heart muscle. And if we transplanted the stem
cells, that decrease in fractional shortening is
blunted. So transplanting stem cells
helps the heart, in that it blunts the remodeling and also
improves the fractional shortening, or contractile
properties of the heart. Two good things.
How does it do it? Well, you know, originally we
were thinking that it was all regenerational repair to help
the tired heart. In other words, we formed new
heart muscle. But over time, it's become clear
that there are many, many potential mechanisms.
And maybe these cells were only really secreting factors that
helped the heart repair itself. Or maybe they're fusing with
other cells in the heart to change their function.
Maybe it's just stabilizing that scar so it doesn't keep
stretching and putting the heart in mechanical disadvantage.
Maybe it's turning on the cell cycle, in other words, getting
those cells that we thought could never divide, to divide
again. Changing the way that the
connective tissue in the heart acts.
Reducing that programmed cell death or drop out heart cells.
Turning on endogenous stem cells.
Forming new blood vessels. They're really many
possibilities that are being investigated, that ultimately
are helping the tired heart. It's really up in the air as to
which are the most important mechanisms, and the most
powerful. But I think this gives you an
idea that there are many potential avenues that will
develop over time to treat heart disease that are really
fundamentally new insights. But it hasn't slowed us from
getting into clinical trials. And these are, this is a list
that I know no one will be able to read.
And I just show it to you to show you how many trials there
have been done since this discovery in 2001, up to 2006,
these are the completed phase 1 and phase 2 trials looking at
cell therapy in the heart. This is really unprecedented to
sort of get some of these trials into patients, these cells into
patients, at this quick tempo. And phase 1 and phase 2 trials
are primarily designed to look at safety at end points, and
less at efficacy. The phase 2 trials start to look
at how beneficial this therapy is.
So the conclusion from the initial trials was that as best
we can see, putting primarily bone marrow cells into human
hearts is safe. These are autologous cells, so
they're taken from the patient, his or herself and put back into
the patient, mostly after a myocardial infarction.
But there's a variety here of different approaches here.
It seems to be safe. Now the larger, the two larger
trials that have been done to look and see if it's more than
safe, if it actually helps. Here's a German trial called the
Repair AMI Trial. They took patients after a
myocardial infarction who had an impairment in the contraction of
the heart. They transplanted these cells
three to seven days after that infarction.
And they looked at how well the contractile function of the
heart improved after that. They saw, shown graphically
here, that there was an improvement in the ejection
fraction, or the contracting properties of the heart.
And they also looked at clinical end points.
In other words, how many patients died, had a recurrent
myocardial infarction or needed to have a blood vessel opened
again. That also was improved with the
cell therapy. And now there's follow-up to
this original study. It was published after one year
of follow-up. At the meeting I was at earlier
this month, now we're at two years follow-up.
And these beneficial effects seem to persist.
However, if you go a little further north to Norway, and you
do apparently the same thing in a trial called the ASTAMI trial,
where they randomized 100 patients after a myocardial
infarction who had angioplasty, percutaneous intervention.
Then they got these bone marrow cells on day six.
They looked at left ventricular function by a wide variety of
measurements. And the long story short is they
didn't see any beneficial effect, either on ejection
fraction or on clinical end points.
So that has left us with some finger pointing going on,
talking about whose cells are better than whose and how you
isolate the cells. And so there is ongoing debate
and a number of articles trying to understand how preparing the
cells after you isolate them from the bone marrow may impact
their biologic activity. I'm not going to go through all
the details of some of these comparisons, but suffice it to
say, there are some fundamental disagreements on the right way
to prepare the cells, and whether that impacts--
Yes? >> When you get a negative
result, how do you know that the cells that you put into the
heart are actually integrated in some way?
So the question is if you get a negative result, how do
you even know you got the cells where you want them, and whether
they're alive and functioning? So that's one of the fundamental
challenges with human trials. It's hard to answer some of
those very logical, basic biological questions.
And I think, again, that's one of the reasons that animal
studies are so important, really, to refine our
understanding. The best we can tell is that
when we put in these cells, we are targeting them pretty
specifically, because in both of these trials, they put them in a
catheter. And that catheter went into the
coronary artery, where the infarction was.
They blew up a balloon, so the cells couldn't go backwards out
of the heart, but only could be shot down the coronary artery
into the infarct bed. So they could only go into the
tissue where there had previously been an infarction.
So they should go that direction.
The question is did they stay there?
Do the stay alive? And we don't know from the human
trials. There's no easy way to track
that. In part, because one of the
reasons this has been able to get to clinical trials so
quickly is that if you take cells out of a patient, the
patient's own cells, you just clean them up a little bit, and
put them back in, there's less chance for things going wrong.
If you take those cells out, mark them with a genetic
approach so you can see where they are and get reporters, then
you've monkeyed with them, you've got to do much more
quality control. So for these first clinical
trials, they're sort of the first gee-whiz approach.
So your question is good, and we don't know.
Yes? >> Do you have baseline data on
the changes in contractility without stem cells.
You know, I went over that. I glossed over that quickly.
That's another great question. It turns out that even without
stem cells, with optimum medical care, with medium sized heart
attacks, ejection fraction tends to get better after the heart
attack if you get on the right medicines and good medical care.
What they're arguing is that there's an even greater
improvement with the cell therapy.
So they've compared it to placebo, which is squirting just
the media the cells were growing in, to the cells.
And both improved relative to right after the heart attack.
But the improvement is even greater with the cells.
Yes? >> What was the change in
ejection fraction? >> It was not too large.
You know, the absolute change was shown here about 2% to
2-1/2%. >> What was the question?
Change in ejection fraction. >> I'm sorry, so what is the
change in ejection fraction? And the question I add to that
is it clinically significant? So a normal ejection fraction in
patients is generally greater than 50% or 60%.
And so a 2-1/2% improvement on ejection fraction some people
would argue is of borderline clinical significance.
It's of statistical significance.
In other words, it seems to be a clear difference.
But will that impact clinical outcome?
People have debated that. But in this trial, they did make
some measurements of clinical end points, suggesting it could
improve how patients did, at least in this trial, with their
cells, in Germany. So there's a lot of question and
debate as far as the right cell preparation and the right
patient population, as well, that will maintain benefit.
Some of the earlier trials studied patients that didn't
have very big heart attacks. And some people have argued that
if you're looking at patients with a small heart attack,
they're prognosis, outlook, is very good.
They're going to do well, regardless of cells or no cells.
So it's sort of silly to study cells in those folks.
So you really need patients that are in trouble, that have
a significantly weakened heart, that are going to need some
additional help. So only now are those patients
being studied. Even though we're still trying
to understand this biology, the trials continue.
And we have been reluctant to get involved, initially.
But now we couldn't hold back anymore.
So we're participating in a trial here.
This trial looks at patient population.
It's a little different. These are folks that have
intractable angina. So they have blockages in their
coronary arteries that we can't fix with angioplasty, with the
balloons, with stents, we can't treat with medicines any more.
They have chronic pain, chronic symptoms with any activity.
So they're really at the end of what we can do with medical
therapy. Bypass surgery has usually been
done, can't do it again. And so these are sometimes
referred to as no-option patients.
And so one of the hypotheses is if these cells can help grow new
blood vessels, and get blood to the muscle that's not getting
enough blood that you might improve the angina.
You might improve the clinical status of these patients.
So there's a trial that Amish Raval is the local principal
investigator. It's a multi-centered trial.
Douglas Losordo at Northwestern is the overall trial principal
investigator. Where we isolate from blood
CD34+ cells. This is a particular protein
expressed on endothelial progenitor cells in the blood
that we can then use magnetic beads, pull them out of the
blood after they're mobilized using this apharesis technique.
And then purify them. Then we take the patient to the
catheterization lab and use a fancy technique of
electroanatomical mapping called NOGA, where we can both look at
the function of the heart, how it's squeezing, as well as the
electrical activity, and identify regions of the heart
that aren't squeezing so well but are still alive based on
their electrical activity, which is a hallmark for that area of
the heart not getting enough blood.
That's shown here in this red area on this map.
And the black dots are where we can inject cells.
So you make multiple injections of cells in this area of heart
muscle that's sort of alive, but barely alive, in the hopes of
getting new blood vessels to form there and improving the
patient's angina. That's an ongoing trial that's
still enrolling patients. We obviously don't know the
outcome of that. But I think it's important to
give us a dose of reality as far as how long we can expect these
developments to take, really, to get into mainstream medicine.
And how much it's actually going to cost.
I think it's useful to look at drug development as a
comparison. So from getting an idea of a
target for a drug until FDA approval of a drug, in the range
of 10-15 years for most drugs. And in current dollars, costing
in the range of $800 million per drug, on average.
A pretty big investment in time and money.
So thinking that we can get the complexity of cells into
broad clinical applications over a remarkably short time period
without much investment is probably not very realistic.
Maybe cells are more like devices, such as the implantable
cardiodefibrillator, ICD. That story, first described in
1969 in an animal experiment in Baltimore.
It wasn't really put into a patient experimentally until
1980. And the first FDA approved
application was in 1986. So there, 17 years, sort of
from the proof of concept until patient application.
What about stem cells themselves?
Well the whole idea of stem cells isn't all that novel.
Blood stem cells, or hematopoietic stem cells,
were really first conceived of in the late 1940s and
early '50s, largely based on our understanding of what
happened after Hiroshima and Nagasaki.
And the radiation sickness and loss various blood populations
in those folks. And so the concept of a
stem cell renewing blood in the bone marrow grew out of that.
And the first successful bone marrow transplant was done in
1956, in identical twins, for leukemia.
But it really wasn't successful in an unrelated donor until
1973. It's become more broadly
available to patients, and there is now banking of bone marrow,
and so forth, and it's a major clinical application.
Again, that took from, really, the '50s until the '80s to get
there. So I think there's a lot of
promise with cellular therapies and regenerative medicine for
the heart, but it's not going to happen tomorrow.
Stem cells has also brought up questions of ethics and where
the stem cells come from. This is largely focused on human
embryonic stem cells since they're derived from the human
blastocyst or embryo. And those embryos are destroyed.
And so this raises questions that have challenged us over
time. What is the definition of life?
And other questions, such as cloning, also called somatic
cell nuclear transfer. That's been suggested to be
potentially a attractive way for what's called therapeutic
cloning. Things like reproductive cloning
are outlawed in most parts of the world.
Also concerns about exploiting oocyte donors, or egg donors,
to be able to generate these cell lines.
And then questions such as chimeric animals.
If you treat an animal brain with human brain cells, what
have you really created there? If chimeric animals go germline
and you have animal and human genes mixed in reproduction.
A clear ethical concern. So that's led to a lot of
discussion, thoughtful debate, and a lot of different opinions.
Ultimately some guidelines have emerged from a variety of
sources. Some of the best known are shown
here. The National Academy of Sciences
has produced guidelines for human embryonic stem cell
research that you can look at. The International Society for
Stem Cell Research has also provided guidelines.
Both have suggested the formation of oversight
committees, an ESCRO committee, which we have here at the
University of Wisconsin, as well as other institutions have them.
Standing for Embryonic Stem Cell Research Oversight Committee, to
be sure that only ethically approved applications are
underway at the university. And different countries have
come up with different ways to provide oversight for this.
And again, what happens in the United States, as far as our
national policy. This is the Bush Administration
policy, as per the Web sites. And it states that federal funds
will be set aside to explore the promise and potential of stem
cell research, with sort of the coda here that federal funds
will not support the further destruction of embryos for ES
cell research. So scientists must use existing
lines, that were derived before August 9, 2001.
So a compromise position by the Bush Administration.
And the funding of more translational, that means
getting from the basic research lab to the clinical arena is not
well developed yet. And that's in contrast to drug
development, right? The pharmaceutical industry has
really developed this structure to get a compound that may be
useful through clinical trials into patients.
Many of the ideas come from basic researchers, but there's
big cost, big funding that comes from the pharmaceutical
industry. There is no such thing yet for
cellular based therapy and regenerative based therapies.
And so this is one of the growing pains that we have to
work with right now with this novel approach.
The federal policy has been a little complicated with the
inability to use newly derived embryonic stem cells.
So some of the states have seen fit to address this issue.
And it's ranged from really trying to facilitate research
using stem cells and embryonic stem cells.
The biggest example is California, which passed
Proposition 71, a couple years ago, that took $300 million a
year of taxpayer money for ten years, or $3 billion, to support
this research in the state of California.
Obviously, they're pretty excited about it.
And if you compare that to the amount of money the NIH spent
in 2006 on stem cell research, $28 million, compared to
the $300 million in California, you can see where the field
is not quite level since this was spread throughout
the country. Other states have provided
initiatives to support stem cell research, while some states have
passed legislation prohibiting it.
So it's a varying playing field out there in the U.S. right now.
To facilitate our work in stem cells and regenerative medicine
here on campus, we formed a center recently.
And our mission is, "To advance the science of stem cell biology
and foster the clinical breakthroughs in regenerative
medicine through faculty interactions, research support
and education." And one of the things that we
realize has been very lacking here on campus is a good way to
communicate, both within campus and outside of campus.
We really need to get better communication.
That's important for you, too, because we have a Web site here
that can provide some of the background, maybe I'll get it up
here, maybe not. No, I've got to log in to the
network. But we have a Web site that
provides information for patients and also general
information about stem cells and the researchers here on campus.
We want to improve the basic research, work to translate this
basic research to clinical treatments, understand the
challenges in bioethics and also develop appropriate public
policy that can really allow this new area of therapy to move
forward. We want to get people working
together across disciplines. Because as you can tell, this is
getting complex. You know, we think of developing
drugs as complex. That's a single molecule.
If you think about the complexity of cells and really,
the tens of thousands of different molecules working in
sync there. It's not a simple process.
So we want to get groups from chemistry, from engineering, the
basic biologists, the clinicians, all working
together. And also we're working hard to
expand our educational activities here.
So just a few things that hopefully you'll be able to take
home. I have to say heart disease is
still a big problem here. It's our number one killer.
And we really are in desperate need of new therapies.
Some of the new tools and approaches that have come
through basic research have allowed us to understand that
there actually are stem cells in the heart.
And I think that's going to provide all sorts of new avenues
for therapy. There are many types of stem
cells that researchers have discovered and are working with:
embryonic, different adult cells, stem cell sources, and
now the newest kid on the block the induced pluripotent stem
cells. These stem cells can self-renew
or divide indefinitely in culture.
They can form the highly-specialized cell types
that are necessary to repair or regenerate a heart, or other
organs, for that matter. And cardiac regenerative
medicine is really a rapidly expanding field.
We're developing new treatments. But it's a long road and it's
going to be years before many of these treatments become
mainstream. And I think this will
revolutionize our treatment approaches for a broad variety
of diseases over the coming decades.
And all the work that I presented was the work of many
folks working together. And I just show you some of
their names. With that, I'll stop and try and
answer any questions. ( applause )
Thank you. >> You referred to embryonic.
But there's also other options for stem cells...
( inaudible ) >> The question is,
I mentioned embryonic stem cells in the talk.
And there are other options. So what makes embryonic stem
cells attractive or not attractive.
The embryonic stem cell, right now, is sort of the gold
standard for a pluripotent stem cell.
That is, it can form every cell type in the body.
Most of the adult stem cells have a much more limited
repertoire. So they can only form a certain
collection of cells. Typically, if you take a stem
cell from the heart or the brain, it's best at forming
heart or brain. The other advantage of embryonic
stem cells is that they're better able to grow in culture,
to renew. So you can grow them potentially
indefinitely in culture, which means you can grow up vast
amounts of cells, which can grow into vast amounts of tissue.
Whereas the adult stem cells undergo senescence.
They stop dividing over time in culture.
So you know, obviously, there's ranges for both of them.
But the attraction with the embryonic stem cells has been
that they're the most versatile cell, and if you grow up the
most of them, and they do best in culture compared to the other
cell sources. But you know, there are
obviously limitations. You don't have unlimited numbers
of embryonic stem cells. They're difficult to get because
of the use of human embryos. So that takes careful
consideration and the ethical concerns with that.
So there are pluses and minuses. >> How is it in...
( inaudible ) Response to these cells, which
came from different individuals? >> So that's one of the
challenges if you're going to use these cell therapy.
We talked a little bit about autologous, self-cells put back
in and allogeneic. So the question was, does it
matter, sorry, I'm repeating the question a little after the
answer. But the question is how does
this impact, if you use embryonic stem cells from one
embryo that's not matched to the patient.
And that is a concern. There is good reason to think
that those cells would be rejected unless we get clever
and find ways to allow those cells to be tolerized, so induce
something that's called immune-tolerance.
We know from work with solid organ transplantation, that is,
kidney transplantation, heart transplantation, there's been
ongoing research to understand how to induce that tolerance so
you can take those cells. The easiest way is to give
immunosuppressive drugs. And we know we've been able to
do that with transplanted organs.
That has some shortcomings, because the immunomodulating
drugs can have some side effects that aren't too desirable.
So I think it will take ways to modify the stem cells, perhaps
to make them better able to be tolerated, as well as, for
example, one strategy is well, if you're going to really do a
lot of cell therapy and repair a heart in a patient, maybe you
also need to give them a new bone marrow.
So you can put in cells and reconstitute their immune system
with bone marrow cells derived from that same embryonic stem
cell line. There are many other sort of
theoretical approaches. >> Theoretically, your own cells
would be preferential. >> That's why there's a lot of
excitement with these, you know, Jamie Thomson's recent discovery
of these induced pluripotent cells.
Then you don't have that immune rejection problem.
And I think that is something that's really going to change
the field. And has a lot of folks going
that direction right now. The limitation is that those
cells are genetically engineered with viruses that came in,
to sort of get them back to stem cells.
So the current generation, I don't think anybody would
comfortable using those for therapies.
Because where those viruses go in, they can alter genes and
potentially lead to tumor or cancer formation.
So this is a first step in the long-term, if we can find better
ways to induce them. I think you're right, that would
be very exciting. Yes?
You mentioned that the current cultured cells that
you're creating can be used for drug reactions.
Have any experiments been done where they've actually tried
that out? >> Well, I showed you one
example there where the action potential got longer with the
particular drug that's known to be an offender.
So we have, in our lab, in the original publication, tested a
few drugs and shown that in a small subset, it has some
predictive value. Of course, the literature out
there, there are thousands and tens of thousands of drugs, so
how good this test is, we really need to go through a lot of
drugs. And that hasn't been done yet to
my knowledge. I think in the back.
With your last announcement, when I was listening on the
national news and reading the national papers, it was always
experts from Chicago or someplace else that were talking
about what Jamie did. The University of Wisconsin was
hardly mentioned. Didn't you guys feel slighted?
Well, you know, the question is...
( laughter ) If you didn't hear it,
with the announcement of the induced pluripotent stem cells,
the experts were not from Wisconsin, talking about it.
And my own impression of that is, is that typically when
discoveries are made, the media, especially big discoveries, like
to get independent, outside experts that aren't tied in to
the research. Of course if you talk to
researchers at Wisconsin, they're going to tell you it's
the greatest thing since sliced bread.
So they want to find a somewhat independent, credible scientist
somewhere else to discuss it. So I think that's driving a lot
of those expert comments from around the world.
And frankly, I'd rather be the institution developing it and
having the discoveries made. Let everybody else talk about
our work here. That's fine by me.
Yes? I think up front.
Is anybody doing any work on stimulating the existing stem
cells in the heart to do the process?
The question is, is anybody studying how to stimulate the
endogenous stem cells in the heart to help repair the heart.
People are looking at that, and are trying to add cytokines,
or signaling molecules that are soluble, to turn on those.
First we have to understand what turns on those cells, and we're
still learning that. Then we have to be good enough
to be able to see that they're turned on and what they do.
So people are looking at that. And part of that is
understanding what's called a niche.
So where those cells live in the heart, and that specialized
environment, and how to foster that.
So people are looking at that. It's not close to clinic yet,
though. Yes, another question in the
front? >> Yes, I thought I heard you
say that NIH was spending $26 million on stem cell
research. If one does the calculation,
that's about what it costs for one hour in the war in Iraq.
I wonder if you could comment on that.
So the question is the NIH is spending $28 million on stem
cell research in the U.S. And that's roughly equivalent
to the cost of one hour of funding for the Iraq War.
And my comment on that is it wouldn't be my choice.
But to comment more than that, I'm not in a position,
unfortunately, to change it. I think over here, yes?
I believe you said earlier that stem cells are circulating.
I was just curious, is there any natural event that takes place
when a tissue is injured that generates a signal that says
it's in need of stem cells? >> That's a great question.
The question is, stem cells are going around in the circulation.
And is there a signal when there's damage to a particular
tissue, come help me out. And I think there is.
And those signals overlap what we've traditionally called
signals for inflammation. So when you have a heart attack,
your heart gets filled up with blood cells, white blood cells
that in part chew up the damaged tissue.
But it's probably also a signal to bring in some cells to try
and help repair it. And it's the same with damage in
other organs. There are signaling molecules
that cause these cells to mobilize.
We don't really understand them too well.
And the real problem is that most of these cells are present
in relatively low numbers. So you know, for example, a
human heart has in the range of four billion muscle cells.
So if you start doing the math, it's hard to get four billion
stem cells into the heart. So you really are dealing with a
very small number of cells with a massive task at hand.
So there are ways to get those cells out, and those pathways
are being dissected out. A question over here?
You talked about heart tissue.
I wondered if you would just comment on clinical trials and
successes or failures on regenerating tissues.
So the question is, I've had a cardiac-centric focus on my
talk. And what's happening in other
tissues. I think as many different
tissues as there are, there are beginning explorations of
clinical trials. There have been some trials in
neuro diseases, primarily Parkinson's disease where fetal
tissue is put in patients with Parkinson's disease.
That was really done in the late '90s, and had equivocal results.
But there are new trials with new sources of the dopaminergic
neurons being considered. There's a trial here on campus
using a human cell line that can form skin in burn patients.
And in patients that have had bad burns that can't have grafts
because they've been burned over 80% or 90% of their body,
they've normally gotten cadaveric skin grafts.
So Lynn Allen-Hoffman is leading a trial where she is taking a
stem cell that she's growing in tissue culture that can form,
they're called NIKS, Nearly Immortalized Kerotinocytes.
And so they can form skin cells, and potentially be used for skin
grafting. There are a variety of
orthopedic applications where stem cells have been used, and
tissue engineering for repairing bone.
There's a variety of other things that are on the drawing
board. One of the ones that I think is
the most exciting is for diabetes.
And diabetes, sort of the proof of principle experiments have
been done, if we can get the right cells to do it for stem
cell therapy. That is, as you may or may not
know, juvenile onset diabetes is due to a loss of functional beta
cells in the pancreas. So they are lost, so you can't
secrete insulin. And so taking islets out of
cadaveric donors, brain-dead patients, and isolating those
beta cells and then injecting them into the liver, actually
through the portal vein, in patients with diabetes, and
immunosuppressing them, so they don't reject those cells, has
successfully treated Type 1 diabetes and the patients have
glucose control. You can take cells from an organ
donor, isolate those cells, put them into a patient and
potentially cure diabetes, with the caveat that you have to be
on immunosuppressives, which is a problem.
But to me, that tells me that if we continue to work with these
stem cells, and can get stem cells that can form these beta
cells, that's going to be a disease that may be amenable to
cell based therapy in the not-too-distant future.
So there's, you know, a vast array.
I can't touch on them all, nor am I qualified to touch on them
all. Yes?
What is the basic difference between stem cells and cancer
cells? >> That's a good question.
The question is what's the difference between a stem cell
and a cancer cell. I've told you stem cells are
great. They keep growing forever in
culture. What could be better?
But I could've said, cancer cells, they're bad.
They keep growing forever. And so they clearly have some
overlap. Most of our stem cell
populations are fairly quiescent in the body.
That's one of the things that defines them.
They don't really divide much until they're stimulated.
They respond to the local environment in their ability to
differentiate and form various specialized cell types.
But cancer cells have sort of lost that check on their growth
control. So they continue to divide.
They don't turn off in response to the signals around them.
There is an emerging concept of a cancer stem cell.
So a cancer stem cell is that cell that's sort of slowly
dividing that can give rise to the new cancer cells that
rapidly grow and cause the problem.
And some investigators believe that really, the failure of many
cancers therapies is related to the inability to get rid of the
cancer stem cell. It's sort of sitting there,
hiding their in the background, and it's the fast dividing
cancer cells we can get rid of. If you don't get rid of the
cancer stem cell, the cancer comes back.
So some of the biology clearly overlaps.
Some of the gene regulation programs, some of the cell cycle
programs, the ability of the cells to divide overlap.
But their behavior is distinctly different.
Metastasized cancer cells sound like pluripotent stem
cells in a way. >> It does.
So metastasizing cancer cells, are they like pluripotent stem
cells going anywhere in the body?
Probably not. These are cells that have some
lineage commitment. In other words, if you've got
lung cancer, these cells have some similarity to lung tissue,
either an epithelial form or a small cell form, a different
form. And when they metastasize,
they still show that phenotype. So they don't go to the liver
and become liver. If they were pluripotent cells
and went to the liver and became more liver or repaired the
heart, that'd be great. But they don't.
They sort of are committed to that lineage.
But they're abnormal in their growth control.
They don't turn off when normal cells stop dividing.
They do clearly overlap. Yes?
I know the brain is not your part of the body, but the brain
controls most of us. ( laughter )
And how does that impact the rest of the stem cells
that they're working on in the heart, whatever they're
working on. >> The question is how does the
brain feedback on other stem cells in the body, and is there
an overriding controller. I think there's no doubt that
the signaling, that the nervous system impacts cardiac function
in many ways. We know that from when you get
excited, your heart rate goes up.
And there are a variety of adrenaline like molecules that
stimulate the heart that may impact stem cells.
So there may be some relationship.
I don't think in general, though, we think the brain has
specific, strict oversight of all the stem cell populations in
the body. At least our current
understanding. But maybe it does.
And as I always tell my neurologic colleagues, the brain
doesn't matter if your heart stops.
( laughter ) I can't understand the brain,
so I worked on the heart. Yes?
Do you think the field of epigenetics is going to have an
impact on this work? >> So the question is will the
field of epigenetics have impact on this.
And so obviously we have an educated audience here.
But for the few that don't know the difference between genetics
and epigenetics, standard genes, DNA, what we've sort of talk
about all the time, we understand that our chromosomes
in our cells have a DNA encoding specific genes that turn on and
off, and create the proteins that are necessary for us to
live. But epigenetics is sort of a
different control mechanism. Sort of modifying the overall
structure of those genes, so they can be turned on or off.
And whether they're methylated, or other impacts on the gene, so
they're available to turn on and off.
And it's the epigenetics that really allows us all to commit
to a particular lineage and not be able to go in other
directions, to a large extent. So I think, especially for the
induced pluripotent stem cells, epigenetics is a giant field
which will be explored, and quite important.
We really don't understand what's allowing certain parts of
the genome to be active in certain cells.
We're learning, and there's a lot of advances, but we're just
starting to scratch the surface, so that will be important.
In the back? ( inaudible )
So there was an investigator here on campus.
Sorry, the question is what about stem cell research and
multiple sclerosis. And Ian Duncan here on campus is
in the Vet school, and actually studies the abilities of stem
cells as a potential treatment for multiple sclerosis.
Multiple sclerosis is an interesting disease in that it's
what's called a demyelinating disease.
So the axons, the particular parts of the nerves that send
out distally, to go to the various parts of the body, are
wrapped in a special sort of insulator called myelin.
And with multiple sclerosis, they lose that myelin and become
dysfunctional. So one idea is if you can get
cells in there that would protect that myelin and
re-myelinate them, you may be able to treat MS.
That's ongoing work. I'm unaware of anything getting
to clinical trials yet, but people are exploring in animal
models the ability to treat MS. >> Thank you very much.
( applause )