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thank you very much for this invitation this is quite unusual because i'm not a
00:00:04
man apologised so i'm i'm an obstetrician i'm on the other side usually um
00:00:15
so um i will try to some might hop because stem cells and worse
00:00:22
um which i think it's quite it's quite interesting because from my obstetrics point of
00:00:27
view and i will tell you how i see the stem cells new field
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no i will not tall ah about how to keep
00:00:38
the placenta because um as an obstetrician i have
00:00:42
to agree to to placenta is one of the most amazing organ switch you will ever see
00:00:47
um so it nourishes the features during the nine months and
00:00:51
then just fifteen minutes after it nourished a child
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it disconnects and calls out i mean this is exciting but
00:01:01
in the placenta we can find a lot of things which might be
00:01:05
interesting in your clinical practised and that's why i will talk about
00:01:10
the stem cells about basic idea what stem cells are
00:01:15
i will talk about stem cells it's therapeutics uh and i will not
00:01:19
go into too much detail um because the next two speakers will
00:01:24
we'll go much more into detail and i would talk about the future with i
00:01:28
think where you should look at and which would change your daily practised
00:01:34
no
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just to give a rock star this is one of my first pictures which i show
00:01:40
when i talked obstetricians about your protection because a lot of them do not know that there is
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a difference between a preterm infant brain and the
00:01:49
term brain uh at term um infant brain
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now if you look at the two pictures you have to imagine
00:01:58
that the injury to this infants would be completely different
00:02:02
and also the to wrap you takes which you will hopefully need some day will be completely different
00:02:10
no path or genesis of brain injury or injury fun obstetrician looks like this
00:02:17
so you have organ and this can be the brain does can be also the long
00:02:22
uh which is developing uh you have injury and you have prepare
00:02:26
so you have the three things which you need to consider
00:02:30
and there's two outcomes can be normal or it can be disease or not normal
00:02:37
and if you talk about therapeutic you always have to consider did you have to three things
00:02:43
no this is not an obstetrics next meeting this is no not allergies
00:02:48
i will show this is how you see the world so
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it's much more complicated you know it's not take out the baby or leave it
00:02:57
you know you have to consider a lot of things
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so this is where clinical player needs developmental biology
00:03:06
so you have first to ongoing development and you have to
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consider that there might be some factors which have already
00:03:14
affected this kind of development and we're talking about in you to wrote
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development so it might be infection there might be genetic disease
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we can talk about a genetic so developmental programming
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and that might be prick conditioning so if you
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encounter a stimulus it can be infection
00:03:37
in the uterus it on the slide infection usually after you were born
00:03:43
you you are much better off when it come to
00:03:47
this kind of stimulus again so it's called precondition
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no you have post new tracks you have nutrition so they had a
00:03:55
lot of things which you need to consider in one of to
00:04:00
interesting things which you have already talked about in the morning
00:04:04
so you talked about lisa so this is the ventilation
00:04:08
so it can be injury but you can also avoided and do a lot of good to do it
00:04:15
too long so and again at the end you will have normal or adverse outcomes
00:04:22
and i will focus on this stem cells now i will focus
00:04:29
on stem cells in a very brought in a very broad sense because
00:04:34
if you talk about stem cells you are user you think about
00:04:38
x. o. janus themselves like like you said the stencil to to
00:04:42
harvest from you try out into my plate on us
00:04:48
but you have to think out of the box they are other stem
00:04:51
cells as well i mean in each of our brains you have
00:04:55
n. do training stem cells and especially in a preterm born infant
00:05:00
the stem cells into super fan trickles on you also might
00:05:06
octave eight so i would take about talk about x. o. train
00:05:10
stem cells which you can use from outside this a therapeutic
00:05:14
and about medication one novel therapeutics we can activate you enter janus that's
00:05:21
so just to give you brought overview there's some difference so when we talk about
00:05:27
injury for example to the brain you can have to adult you can
00:05:33
have a new born and we know that there's the stem cells when when you
00:05:38
use from outside this attribute it's a therapeutic so
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exciting stands up the each tune neural regeneration
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read used in for volume and usually you have an effect on the
00:05:51
brain but you also have an effect on the immune system
00:05:56
and this is what you have to understand that if you use the stems that's the do not call the brain and stay in the great
00:06:02
usually you haven't bystander effects okay they affect the immune system and therefore
00:06:08
make these changes and in the adult oriented newborn
00:06:13
usually you have a local effect so you usually set the affect the
00:06:17
brain now if you look in the in mature in front
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there is always a global disease so it's not just the disease of the
00:06:26
brain is not just the disease off long it's always a combination
00:06:31
and therefore to to wrap you take should also affect not only the and the janus
00:06:38
organ like the brain or the the long but the whole immune system
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and there are differences between in a mature infant and a
00:06:50
newborn infant interns off the immune system because it's neat
00:06:54
still to develop the you have usually growth directed development
00:07:00
so if you consider for example the brain um
00:07:06
the development of the brain is finished when you are forty so last year
00:07:13
uh_huh uh i know some might consider
00:07:18
there's some men
00:07:20
which they never reach it yeah it's also possible but it takes
00:07:24
forty years to develop and mature brain now the most
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intensive development is between twenty four weeks in the first two years of light
00:07:35
now in terms if you look at the signal sell so you have to
00:07:39
the the stem cells in the brain they give rise to the new rounds
00:07:43
which me to go to the right place at the right time
00:07:47
in about forty percent of the neurons will die and it needs to
00:07:51
be cleared out so the immune system in this symmetry infant
00:07:55
it's always activated in the brain because it needs to clear out
00:08:00
all the cells which are dying which is physiological in the process of to development that's why
00:08:07
most of the therapeutics which you will see coming into the clinical practised
00:08:13
act on the immune system because you always have high activation of the
00:08:18
immune system in case of injury and you need to reduce it
00:08:24
no this is what's interesting for me did you ever hear p. i. f.
00:08:29
not yet but today so p. a. f. it's called pretty implantation factor it's also
00:08:35
a factor which produced by the placenta which might be
00:08:39
coming into clinical practised in a couple of years
00:08:43
so for us on the stem cells so stan since i'm not
00:08:47
efficient anymore so nine years ago when you paid a
00:08:50
lot of money to get to stem cells harvest that you had a vision that you might use it some day
00:08:58
if you look at now today they're twenty three trials on stem cells inseparable policy
00:09:05
so it's gonna be coming into you daisy proactive stance says
00:09:10
i advancing more and more now what a stem cells
00:09:16
stem cells i call them they uh doctors without borders
00:09:21
so uh cells which will go to the injury side and depending what what
00:09:26
kind of organ you are or where you are in this in this
00:09:32
a line so hopefully your somewhere down here and they work differently
00:09:38
so um if you and and phoebe and and you lose one arm
00:09:43
you and the janus themselves would be activated and it will grow back
00:09:47
now in case of humans you don't see it a lot but it's still can't happen so for example in the features
00:09:54
if something happens to the thing off to features in twenty four twenty six week in you to row
00:10:00
when it's boring to have a new finger so in in a certain degree
00:10:05
you see this new row or does regeneration uh a potential now
00:10:12
this was stadium nine years ago on nineteen years ago if
00:10:15
you use stem cells they were regenerate the organs
00:10:20
no it does not work like this because we're too complicated it does work in the
00:10:25
skin so this is what you see every day if you have a cot
00:10:29
it will be replaced it issue are being replaced by stem cells but
00:10:35
what in terms of your field what makes them so special and a
00:10:39
lot of stem cells and most of them have this for
00:10:45
different potentials and this is what you need to remember if you talk about the stem cells
00:10:51
these are cells we can try once differentiate so from
00:10:55
one cell type you can in the right condition
00:10:59
in the right time you can push them into completely different cell type
00:11:05
what i think is most important part is they have the ability of full meeting so
00:11:11
they go to the side of the injury uh for example if you had a
00:11:15
brain injury you do not actually need to put ten into the brain
00:11:20
you can put them into the nose and they will go to the bright you can put in entrap original or you can put
00:11:26
him into the vein induced to go to the side of injury
00:11:30
so this is very important this is homing in migration
00:11:35
now how do they work they do not replace the dying cells which we
00:11:40
hoped for in the beginning but yeah secrete ink on one side
00:11:45
a lot of factors which keep the interrupts cells
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of push them into more into survival mode lose and on the other side they have the immune suppression
00:11:58
so the immune system which is activity will be suppressed and in terms of image for instance
00:12:05
or newborn infants this is the most important aspect of this else
00:12:15
how if you're a clinician inch i think most of you are clinicians so
00:12:20
you take care every day of this kind of page which are of
00:12:25
hi risque think this kind of injury like brain injury along injury p. p. d. and so on
00:12:32
now in terms of a clinician if you think this baby needs medication you need it now
00:12:39
so lacking hypothermia you have a window of opportunity you do not have
00:12:43
too much time no if you farthest to sell us from doing
00:12:47
biblical cord and it can be the blot can be the core
00:12:50
itself to tissue it would take two weeks to make them
00:12:55
great approved for for clinical use so in my point of view and you know um
00:13:03
very interested what you gonna say but mine point of view this
00:13:07
stands that's a very interesting interesting that a. t. and
00:13:11
it's not gonna be the stem cells itself which we you going which we uh you gonna be use ink
00:13:17
it will be the stem cell products so the so called vested cults
00:13:23
so if you have it on a cell and this is and isn't kindness then fell it would produce testicles
00:13:31
which may contain proteins d. n. a. r. n. a. on on coding d. n. a.
00:13:36
and then this protein the sexism so testicles would travel
00:13:41
to the recipients else now this messy calls
00:13:46
can be put in the vial and in the fridge so if you
00:13:50
need it you can use only divest tickets and this is where
00:13:54
right now a lot of research is going it's going not to work to sell it sells
00:14:00
but just to sell products because it's much easier to use it in kleenex afterwards
00:14:07
then the whole sell you just to say take the product of the cell
00:14:12
so the future from my point of view our device sickle based therapies
00:14:20
no part of our research is in this part and we use animal
00:14:24
models and the other part is about pretty implantation factor so uh
00:14:30
re implantation factor was discovered about fifteen years ago
00:14:35
um it's called pretty implantation factor because it was discovered by ear
00:14:40
guy who was working in reproductive medicine so he looked at last assist
00:14:46
and he found a small peptide which is being produced and if
00:14:51
u. s. l. produced is kind of peptide you would
00:14:54
get pregnant if it will not produce it you would not get pregnant so this will all i. d. f. pregnancies
00:15:01
so we know that the pretty implantation factor is is
00:15:05
as i said the peptide which is essential for travel blast innovation and phone embryo development
00:15:12
so you can find it in nature you can measure it in every pregnant woman you can measure this factor
00:15:19
now from my point of view it's very interesting because you can
00:15:23
use it as a synthetic clark so it's a small packet fifteen amino acids
00:15:29
it's safe because it's a pregnancy pregnancy the right product and it has been
00:15:34
use four million of years so you can find it in humans you can find it
00:15:39
in the most you can find in a cow all mammals produced expect that
00:15:44
now we have used is peptide in p. v. l. model p. via this
00:15:48
perry ventricular come uh let's see uh so the white matter disease
00:15:52
and this all animal models so you induce injury in this
00:15:56
animals and use this drug soup get any sleep
00:16:02
four seven days this is an example for new rome so you see
00:16:06
here when you're in some missing if you use p. i. yet
00:16:10
then the nuances safe or you see a microbe leon so the activated immune system in the injury
00:16:16
if you use p. i. have then it's restored this is an example of the
00:16:21
cortex it's you know the cortex at different players and the first slayer us
00:16:26
which are born aboard he on the lake las uh the outside players
00:16:31
and again in the injury you see that the outer layers
00:16:34
ah stretched the inner layers i enjoy it if you use p. yeah yeah if you see
00:16:40
uh your protection so this was kind of very interesting observation
00:16:44
which we see it's a saw at the beginning now
00:16:50
from a clinical point of view a lot of drugs do not make it too clinical use because they
00:16:55
do not tested lot rain area and we could see them we can detect this is yeah
00:17:01
you mean he uh he's the kind of strange you can detect
00:17:03
it into the in the brain after you injected septic chemistry
00:17:10
now as i said i would talk about the indigenous stem cells now because
00:17:15
this peptide that t. i. f. it's and so it's uh uh
00:17:20
evolutionary conserved peptide and we saw a lot of effects on
00:17:25
the neural cells on the migration of the cells we
00:17:29
looked at the end of janus themselves if this peptide
00:17:34
affects this kind of stance as as well so
00:17:37
the blue one the other just sells the right ones are the stem cells which are travelling
00:17:44
so you can in the mouse you can mark the stem cells and look after two three four days and
00:17:50
see what happens to the cells now so in the first got you see decide the normal cells
00:17:57
okay i sixty seven all the cells which are proliferating and
00:18:01
mash up the cells which that differentiate oh this
00:18:04
is the normal mouse if in the normal mouse you use l. p. s. l. p. s. is uh
00:18:10
people probably somehow right so this is the protein membrane from e. coli so
00:18:15
it didn't uses inflammation you see much more red dot it means
00:18:20
if you have injury so if you have colour you are in a um yeah i'm i'm united sorry
00:18:26
for you have sepsis the end to janus stances will be activated so it's the nature way too
00:18:35
to to safe oh to conserve the brain it activates the entertainers stands out
00:18:42
now if you use p. i. yeah so this is the third one
00:18:47
you not only activate distances but you see that that differentiating so you
00:18:51
are affecting their calls the uh the fate they um much rating
00:18:57
and one of the ways which we have discovered how we does it
00:19:02
it's by affecting h. nineteen h. nineteen is the known coding are in a
00:19:08
so it's a it's a product in the cell which if you run it into said it does not produce a peptide so
00:19:15
it uh proteins and it's not like an m. messenger are
00:19:18
in a but it's a regulatory peptide and it's heidi
00:19:23
expressed during pregnancy and afterwards you don't see it in now
00:19:28
on most no organs so and we we you know
00:19:31
we could show that this is one of the peptide with p. i. yeah this effect and so um
00:19:39
just one more on this is a and there i so you can also run and i'm ryan the mouse
00:19:44
and see how the injury looks like so again in the injury you
00:19:48
see that the court fixes destroyed and if you use yeah yeah
00:19:51
it saved so at least in the animal models that pretty implantation factor works quite a bit
00:19:58
so to put it together do i think that the m. s. c. some as income is then so stand
00:20:03
sense or p. yeah yes out that the magic bullet is it something that you will use every day
00:20:11
so i think i would consider them a helping
00:20:15
hand from the bystander so this is something
00:20:20
which will affect the and the genius regeneration system both of them the immune cells
00:20:28
in summary i would say that they they make sure infant it's a
00:20:33
complex syndrome it's a complex disease and therefore if you need to
00:20:40
use therapeutics in this infants you meet to have an innovative approach
00:20:48
i think the basic idea of using stem cells or p. i.
00:20:52
a. f. is very promising we still don't know which goes
00:20:57
which application route we still don't know if we should
00:21:00
combine them with other treatments like hypothermia indeterminate fund
00:21:06
and i think it's not a magic bullet yet but this
00:21:10
therapies especially divest tickles or p. yeah you have
00:21:15
a very promising and they're approaching more and more you have the correct it's thank you very much
00:21:27
hi thank you very much martin for use
00:21:31
lose should be for torque already questions
00:21:40
maybe maybe one question you would talking about what he calls you read the order the way to go
00:21:48
already slightly to the t. v. news deceiving or can
00:21:51
you use my basic tools for somebody else to
00:21:56
uh there you hum so they're not specific for the
00:22:01
individual so that's why i mean you can
00:22:05
you can you harvest sells some no i could use the cells of your child
00:22:10
um prepare them and harm is the best because and use it for everybody out
00:22:16
you know they are not no consideration about infection
00:22:19
disease about uh uh brian's about uh using
00:22:24
um for example if you try to cells you use su room and
00:22:30
assume comes from animals user usually from uh uh from window
00:22:37
cow so i don't know if i want to use a cell
00:22:42
in my child if i'm not too it's safe that one device it goes
00:22:46
one once you far this than you can prepared in very early
00:22:51
um but still we do not know know will the will you harvest infirmity mature infant
00:22:57
for mature instant would it be the same for the brain as for the long
00:23:02
and do you need to talk to sit from biblical cord cells
00:23:06
or from you fat cells of full bone marrow or from
00:23:11
oh that missing constants and so they a lot of questions which need to be addressed first
00:23:16
but at least from a clinical point of use it would be much easier to use them as themselves
00:23:24
okay thank you very much the big we humble thanks very much more

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Conference program

Opening
Matthias Roth-Kleiner, Lausanne
16 Jan. 2018 · 9:34 a.m.
Welcome words
Mathias Nelle, Bern
16 Jan. 2018 · 9:36 a.m.
Personalised prediction of weight changes in the first week of life
Severin Kasser, UKBB
16 Jan. 2018 · 9:41 a.m.
Neurofilament serum levels as biomarker of neuronal injury in very preterm born infants
Antoinette Depoorter, PhD Candidate
16 Jan. 2018 · 9:49 a.m.
Neonatal red blood cell (RBC) transfusion practices in Switzerland
L. Gosztonyi, C. Rüegger, R. Arlettaz, Neonatology USZ
16 Jan. 2018 · 9:58 a.m.
NEO (Neonatal Esophageal Observation) Tube - A feeding tube with monitoring function
Patrizia Simmen, Department of Neonatology, University of Basel Children's Hospital
16 Jan. 2018 · 10:25 a.m.
Less invasive surfactant Application - Pro
Angela Kribs, Köln (DE)
16 Jan. 2018 · 11:33 a.m.
Less invasive surfactant Application - Contra
Sven Schulzke, Basel
16 Jan. 2018 · 11:51 a.m.
Q&A - Less invasive surfactant Application
Panel
16 Jan. 2018 · 12:14 p.m.
Stem cells and birth
Martin Müller, Bern
16 Jan. 2018 · 2:32 p.m.
Stem cells and white matter disease
Raphael Guzman, Basel
16 Jan. 2018 · 3:16 p.m.
Protect the neurons: The challenge of the neonatologist and the researcher
Anita Truttmann, Service de Néonatologie, CHUV
16 Jan. 2018 · 4:12 p.m.

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