Bringing brain cells back home | Jocelyne Bloch | TEDxCHUV

This talk was given at a local TEDx event, produced independently of the TED Conferences.
Could you imagine that our brain cells are able, after a journey in the lab, to come back home with a precise mission: to help our brain recover after stroke?

I would like to share with you today

a very interesting experience
I had in my neurosurgical life.

I am a neurosurgeon,

and I have to deal
with human tragedies daily.

It's a real disaster to see people
after a car accident or after a stroke.

If you have a big part
of your brain that is destroyed,

unfortunately, the central nervous system
has very little ability for self-repair.

One of my neurosurgical dreams was
always to try to give back a function

to someone who has lost it

because people remain
severely handicapped,

and it's revolting to see that every day.

So that's probably
why I've chosen this specialty

called functional neurosurgery.

Functional neurosurgeons try

to give back functions or to improve them
through surgical strategies

like deep brain stimulation, for example,
that's the most famous strategy.

14 years ago, I participated

in a major discovery that, in my opinion,

would have an important impact
on the patient's recovery

after a major insult
to the central nervous system.

That's the story
I would like to tell you today.

Before telling you the story,

I have to introduce you to
two very important and different actors;

without them it'd never have been
possible to have this story today.

The first one is not in the room.

You can understand why.

It's not exactly this cow,
but she represents her cousin,

the South American cow.

Without the serum
of this South American cow,

we would not have been able
to grow adult brain cells.

The second actor, he is not in the room,
but he is not eating grass.

He is my very good friend
and collaborator, Jean-François Brunet,

who is a biologist and without
whose patience and pugnacity,

we would never have been able
to grow brain cells.

So now, let's go back to the story.

You have to imagine
that about 14 years ago,

I was a chief resident in neurosurgery,

and chief residents work a lot,
day and night, doing a lot of emergencies.

And sometimes, during these emergencies
you have to remove a piece of the brain.

It's not for fun, it's because
someone had a car accident,

has a swollen brain,
and you have to do craniectomy,

otherwise the patient is going to die;

so, sometimes, you have to
remove a piece of the brain.

And we thought with Jean-François
who is a biologist in his lab:

"Why shouldn't we do something

with these pieces of the brain
that we have to sample so often?"

Jean-François and his patient said:

"I'm sure I am going to do
something very interesting with that."

He tried with different types of serums,

and he saw, finally,
after many, many attempts,

that the serums from the cow
I introduced to you previously...

One day he saw that under his microscope.

And you have to realize
is that this type of culture

really looks like a stem cell culture.

But you also have to know
that at that time, 14 years ago,

we thought that the only stem cells
we have in the central nervous system

were really deeply located
in the brain in two very small niches.

But here, Jean-François with any type
of samples he got from cortex,

got this type of cells,
which was incredible.

And what you can see,
on this type of cells,

the green cells here are astrocytes

those are the cells that are supporting
the neurons in the normal brain,

and inside these little round cells are
immature neurons, immature little cells

that could turn into mature cells.

So when we showed that
to people at that time, they said:

"That's not possible to have stem cells
in this type of culture from the cortex,

you must have taken some stem cells
[from the cortex into the culture]."

We said, "No," because they
do not behave like stem cells,

they divide much more slowly,
and they never form tumors,

and they are really more indolent,

and after awhile, 10 or 15 weeks
of culture, they also die.

It's not like something
which is renewing and renewing.

Finally, we realized
where these cells came from

- because they were not coming
from stem cells -

these blue cells you see here.

All of you have these cells in your brain.

And that's something
that was discovered quite recently.

These cells are called
doublecortin positive cells.

They are very abundant in fetuses

because they help the formation
of the folding of the cortex.

Our cortex is like a folded structure,
and these cells help with that.

But we thought
that they disappear in adults,

but we discovered more recently
that it was not true.

4% of the cortical cells are
doublecortin positive cells.

We don't know what they are for.

Or what they are.

Do they help us when we have a lesion
somewhere? We don't exactly know that.

But what we know is that from these cells

we got this cell culture
that I showed you.

So of course, when biologists
work with neurosurgeons,

neurosurgeons are always very pragmatic:

"Wow, that's a great source of cells.
We may do something."

I told you that we are so frustrated

because the central nervous system
has so little ability for self-repair.

Maybe we've found
something to help our patients.

We thought a little bit,
and we came up with one concept.

Why shouldn't we take
a biopsy of one individual?

-Because we know how to do it;

we put these cells in culture
- we know how to do it -

we labeled the cells,

and then we re-implant
the cells somewhere else in the brain.

Great. Let's do it.

Of course, you can't do it
on a human first,

everybody knows you have to
do it first in a rodent model.

But unfortunately, rodents don't have

these double-quotient
positive cells in their cortex.

We don't know why,
but a rodent doesn't help us.

So we had to find
another type of animal to work with.

Fortunately, we met...

- I already knew him, he was a good friend
and he believed in our concept -

Eric Rouiller, Professor of Physiology
in Fribourg, who has

the biggest monkey facility in Switzerland

and he helped us.

He said: "Your concept is great,
I believe in what you are doing.

Try with these two monkeys."

We were very excited.

First we could prove

that we were able to do exactly
the same culture as that in humans,

because monkeys have exactly
the same cell composition as us.

Then, we did the cell culture labeling
and re-implantation.

The first question we had was:

how will these cells behave,
if are re-implanted in a normal brain?

What will they become if are re-implanted
in a lesion or close to a lesion?

Very interestingly, when they're implanted
close in a normal brain, they disappear.

It's as if you take a biopsy,
you take the cells out from their home,

you put them in culture,
re-implant them in the same individuals

- so you don't have immunoresponse,

they recognize they're here,
but they see the space is already busy,

so they say: "I am not necessary
here, so bye-bye, I go."

But if you implant them close to a lesion,

they go back home and they say,
"There's an empty space,"

they start to accommodate,

and it would take them
a month, a month and half,

but then they start to grow
and become mature neurons.

That was exactly what we saw three months
after a re-implantation close to a lesion.

You see these red cells
which are those we re-implanted,

and note they are not little round cells
I showed you in the beginning,

but they are bigger neurons with axons;

we were under the impression
that they recolonized the area.

We could also prove very nicely
that these were the same cells

we had used in our culture.

Because here you see here that's the dye
we use in our culture, the red dye,

while the green dye is
the marker for the mature neurons.

So you see that these two cells
have a double labeling:

it means there are both green and red;

it means they are mature neurons
that were previously in the culture,

as immature neurons,

and they turned into mature neurons.

Of course what is the next step?

Especially for a neurosurgeon, you want
to know what the implications are:

Is it working? Is it good
to have these cells in?

So that's what we did.

What we did was we trained
a few monkeys to do a specific task

- to take and grab some food pellets
in a drawer on a tray -

and they were really good at it.

It took some time to train them well.

They reached a very good level
of performance.

When they were stable
at this level of performance,

we performed a little lesion
in the central motor cortex

corresponding to the hand motion.

So of course, immediately
after that, they are plegic,

they can not move the arm any more;
they are not able to do the task.

But nature's done quite well.

We are able of recovery,
spontaneous recovery,

- probably due to the spasticity -

and performance becomes better
but only to a certain extent.

So they are able to so something
but not as well as before.

At that stage, we took the biopsy,
we did the culture, we re-implanted.

And what we saw,

and I think this picture
is better than any graph...

So you see, on the left

there is the money at the end
of his best recovery,

when he has spontaneously recovered.

On the right, a monkey
two months after re-implantation.

So all the monkeys we re-implanted

performed better than those
that haven't been re-implanted.

Well, I think it's a nice story.

So now what is the next step?

Of course, we have a lot of experiments
done, with different models,

and we have understood
many things since then.

But still, my aim, and from the beginning
of my talk, is to apply this to humans.

I must say that enthusiasm
decreases a little bit

when you realize how difficult it is
to go through all these processes.

And to obtain the authorization
to go into human trials.

But, I still hope I'll be able
to do it before I retire.

Thank you so much for your attention.

(Applause)