Player is loading...
Stem cells and white matter disease
Raphael Guzman, Basel
Tuesday, Jan. 16, 2018 · 3:16 p.m. · 23m 34s
Embed
Transcriptions
Note: this content has been automatically generated.
00:00:03
thank you very much um thanks a lot first of all to the organised for inviting you also sent to this uh
00:00:09
meeting it's of pleasure in under a in you will wonder what
00:00:13
in your surgeon does here uh in a as mentioned time
00:00:18
and mainly focusing on production you also do that means i am in close contact
00:00:22
with the new born and the prenatal and as you all know all
00:00:28
yeah
00:00:29
we have these problems in the in the in the new donate especially into premature babies into ventricular hemorrhage
00:00:36
and uh i don't need to tell to this old in that it's a big problem sometimes when i
00:00:40
talk to you also turns on your scientist i have to tell them it's a big problem
00:00:44
incidence is not that law was you know and the d. effect of having that hemorrhage is devastating
00:00:50
so this is one of the uh groups of patients were treating and it will
00:00:57
i guess
00:01:01
now what can we do what can i do besides the a
00:01:04
treatment that you do as a unit lies you and physicians
00:01:09
i can do maybe we can was the one true to a potential hydro set for this in the new born
00:01:15
i can maybe do some endoscopy and maybe do something trickle irrigation or uh
00:01:21
trying to take out bought clots but but let's be frank and honest i'm frustrated
00:01:26
was primitive treatments like this site it's not how we gonna really change the outcome of these children
00:01:32
and so obviously when i see him arise like this uh and
00:01:36
mariah of uh uh hypotheses ski weekends to follow puffy
00:01:40
or in the torah born baby yeah east gimmick stroke and does
00:01:44
all the tried we need other treatments especially as a surgeon
00:01:49
you know we think mechanically but we really need to sink not mechanically and go to biology
00:01:54
and maybe there will be new was surgeons inched injecting status as i'm not excluding that
00:01:59
but definitely there's gonna be more interesting sings and then doing surgery for at
00:02:03
least for these patients so one of the problems i'm really interested
00:02:07
in is what do we do with white matter disease and what we
00:02:11
need for the development of white matter actually in the developing brain
00:02:15
so we need first of all these only got dental side progenitor cells
00:02:19
or to stem cells that will eventually maybe my the nate
00:02:22
um uh x. owns a so here the neural will sell was an x. on
00:02:27
and we have a proliferation of these are all the good dental sigh progenitor cells
00:02:32
that will become a so called pretty mine innately good
00:02:36
intro site it's kind of a step in between
00:02:39
to becoming that might be making really good intro sites that will eventually be up to the minute she
00:02:44
now the mining she does not only here uh uh to have rapid firing of
00:02:49
electrical activity it's also here to protected yak stones and to norris jackson's
00:02:54
so without the mining sheet in in in a primitive way the axles will actually degenerate
00:03:00
and we get colour younger generations so we have the generation from
00:03:04
the accent to the soul money ronald cells will die
00:03:07
but maybe at the beginning we have a problem of uh only got
00:03:10
into slide projectors and what's very important in the context of days
00:03:14
is that it has been shown multiple times that he's oh piece easily
00:03:18
get intersected only just cells are especially vulnerable to hype box though
00:03:23
so they're more vulnerable actually as a new runs for years we have focused on your ones but it looks like they really are
00:03:29
might actually bought him be more vulnerable to disciple seek a event
00:03:34
and so we're trying to think about how could be
00:03:37
you know protect those all p. c.'s replace or help indoor tennis and i agree with that
00:03:44
doc tomorrow talk before how can be protector promote androgynous repair mechanisms
00:03:51
uh another point more on the microscopic and clinical level i wanna mention is that these
00:03:56
are the patients i we'll see later on once these patients if they survive
00:04:01
uh i will grow all day develops herbal poll the which is a big name for
00:04:06
a lot of a fee not types but what has been shown amongst other things
00:04:11
is that a using diffusion tense re emerging so it's m. r. i. methods to show like mad attracts in the brain
00:04:18
looking at a kid children with cerebral palsy you see that
00:04:22
there is a correlation between the cortical spinal tract development
00:04:26
and the disease severity so if we call goal from
00:04:30
the most c. viewer patient was quadriplegic cerebral palsy
00:04:34
to a normal and healthy age matched control a we see that
00:04:38
there is a a a correlation between mike white might attract
00:04:42
uh information and and disease severity with the
00:04:47
type e. g. a cerebral palsy patients
00:04:49
uh being in between so there is obviously in effect on white might attract
00:04:54
uh and so the question here is how can we preserve how can regenerate
00:04:59
that is why might attract so my lab is focusing a little bit on these white matter a great generation
00:05:06
before i go into a talking about a a lab data from my lap
00:05:11
i'm just showing days and we have forty three times now i think
00:05:14
we started to stem cell field uh and twenty plus years back
00:05:18
thinking that you're gonna replace the cells obviously is the same for the long and the
00:05:22
same for the brain they were transplanting cells neural stem cells in the brain hoping
00:05:27
that they will actually replace the brain but it was always a big discussion how can
00:05:31
these hundred thousand cells that we transplant prepare millions of cells that the generated
00:05:36
and still get the clinical effect and so many and and and myself to in the in the in the scroll food
00:05:42
uh back then it a while ago said well we're going really from cell replacement uh to traffic
00:05:48
support so we think that the cells that to transplant actually helped the androgynous repair made mechanisms
00:05:55
being a temple adjust your janice is being it uh in your remote elation
00:06:01
so here's the questions her we're asking we have a complex
00:06:05
a half way from normal my benighted uh x. on in the brain and
00:06:10
this could be spinal cord as well we're talking about right now
00:06:13
two degeneration again this can be used to hype boxer but there's obviously other
00:06:18
diseases that would lead to the generation of the nineteen and to
00:06:22
read generation and we have the simplify the parameters that has immune cells
00:06:27
or the brain resident microbial which of the brains immune cells
00:06:30
we have peripheral immune cells macrophages first neutral feels
00:06:35
uh and then uh and one acidic macrophages that invade the brain and uh it cleared it really
00:06:41
and we don't need to read generative capacity which is formation of for the good dental sites that are supported
00:06:47
by astral sites uh there's a big focus now coming on astro size that were neglected for many years
00:06:53
that will actually will help prepare in this mechanism at these my dingy
00:06:58
and so the question is how can we influence this
00:07:02
mechanism using exhort generous themselves that are transplanted
00:07:07
so just very briefly too few of the methods were using i have been mainly working with
00:07:12
new room eurotunnel stem cells so this is feet in your own little stem cells
00:07:17
not much the kindest l. says but a lot of things i talk about the plight amazing times then says as
00:07:22
well we haven't unit to hypothesise schema model which is consisting
00:07:27
of corrupted like asian and that will tick exposure
00:07:32
we do a lot of intro vascular said delivery using a um by luminescence uh
00:07:37
to control what sells are going so we have reporter cells expressing see phrase
00:07:42
uh we do i mean imaging your diffusion tents were imaging
00:07:45
and then gene expression uh end in in vitro studies
00:07:49
so just to show on again i think this is important and it was a mentioned by the two speakers ahead
00:07:56
even the neural stem cells that injecting the body and this is by luminescence
00:08:00
over time so one day after injection ten days after injections most
00:08:04
of these cells will actually disappear with time so they're not actually integrating
00:08:09
in the brain some might actually integrate but you see here
00:08:12
early on we have holding of the cells it was mentioned holding two injuries important
00:08:17
but seven days later we will have only few cells and if you go further on actually almost no cells device
00:08:24
despite this what you observed is a tremendous effect on the brain so here you have saving treated
00:08:30
animals sell treated animals high resolution camera i you see cortical injury people competent to read
00:08:36
i mean this that treated animals we do not have a last
00:08:39
digit integral but we have a protection a off the host
00:08:44
this is the food intense religion of the right brain and you can appreciate that
00:08:48
you have a very blues formation of white matter he does is all white might attract whereas in the cell treated animals
00:08:54
you have a regeneration at the vista logic level just briefly a measured
00:08:59
in the cortex corpus colours in different areas of the brain you
00:09:02
can actually measure that you have a significant difference in my the nation
00:09:06
that smiling basic protein staining between seven say line treated animals
00:09:11
uh and you the controls that obviously are better so you have a tremendous effect despite only
00:09:16
having a few cells and during the brain first of all and even less actually surviving
00:09:22
and what we found when we went to okay what's going on we send gotten us all the good and the genesis
00:09:28
we found that you have a significant up regulation of indoor just your genesis so new born cells in the brain
00:09:35
and of those we have a significantly increased only got
00:09:39
intro side proliferation so o. p. c. proliferation
00:09:43
uh here by histology we also have an increase in maturation of these
00:09:47
o. p. c. to my the native only good intro sites
00:09:50
so what did we do we affected the androgynous repair mechanism to
00:09:53
we did not replace but we improved the androgynous repair
00:09:59
um you can see now in v. troll and that's uh from the start in two thousand
00:10:05
and i'm a cells in vitro and we have done the same was neural stem cells
00:10:10
uh only got entrust type a progenitor cells exposed to
00:10:13
oxygen to call deprivation which is like ipod stuff
00:10:17
and then protection in this example by human umbilical cord uh about stem cells so there is a
00:10:23
protective effect also in vitro all uh when we look at high pulp seek a challenge
00:10:30
so i'll just briefly few results on the effect of stem cells only good
00:10:35
intro sides now one of the big topics it's him is immune modulation
00:10:41
when we look at brain morphology it's fascinating to see that
00:10:45
a microbe lee out the brains resident immune cells are in
00:10:49
very close contact a neural stem cells so this is
00:10:52
a a trans jenny can emails that is expressing g. f. p. uh on the uh and my probably are
00:10:58
and in red you have your own all cells in blue you have asked to sites so d. sounds are really intermingled
00:11:05
this can not be a coincidence there's no coincidence in the brain
00:11:09
i think there's a reason they're so close together and
00:11:14
my probably uh uh you've however you've heard before is kind of this cell is it a friend or
00:11:20
is it the fall is it actually helping or is it a detrimental to the brain and obviously
00:11:26
there is so many mike firmly and the brain there needs to be help it can not just the fall
00:11:31
uh obviously and so i will start with some of our studies this was a a word
00:11:36
by a a p. h. d. student of mine could demonstrate it didn't the troll
00:11:42
and user currently running enviable studies that in coke out for experiment
00:11:47
if you take some ventricular zone a stem cells in vitro
00:11:51
together with my crudely out and you eliminate the microbial by killing selectively the my crudely are
00:11:57
the amount of new rust years that's how neural stem cells grow in the dish will actually decrease
00:12:02
sold the neural stem cells to proliferate in the dish if you don't add a lot of factors
00:12:07
actually do we need to do my crudely are at least in this in vitro setting
00:12:12
this is another work we did a few years back to see the other way round how do stem cells influence my crudely ah
00:12:18
and a in a very short summary what we found is that androgynous themselves
00:12:24
but also exhaustion is euro progenitor cells secrete factors that will increase microbial
00:12:30
function a boast proliferation migration factor civic activity and i think this
00:12:35
is especially important not in the acute setting but in
00:12:38
the chronic regeneration of the brain we do need the microbial
00:12:42
both uh support but also to clear that really
00:12:46
eh and we found actually that it was mediated through that jeff so if you
00:12:49
take that jeff away that is secreted by stem cells use that effect
00:12:56
on the other hand my actually as the fall when there's many studies
00:12:59
there's many more studies showing to follow side inject you'd setting
00:13:03
if you eliminate a or down regulate microbial activity like
00:13:07
in this first start here was working jamieson
00:13:10
kind of stance as you can at ten way to micro deal activation after hypotheses scheme yeah
00:13:15
or the study here showed a negative correlation between the amount
00:13:20
all of my crudely uh in the brain of the amount of my pretty uh
00:13:23
that are present versus survival awfully good intro side to generators else inverse correlation
00:13:30
so it seems to be a by face it to a time line where early
00:13:34
on microbial might be detrimental but later on microbial is needed for a generation
00:13:42
not to forget about uh experiments outside of the brain and i'm a big
00:13:46
believer in yeah yeah the connection between the organism in the brain obviously
00:13:52
yeah there is a close talk between the two so what happens when you inject themselves in the tail paint
00:13:58
eh and this is again my report or cells take vine they all end up in the long
00:14:03
pretty much no cells go to the brain versus when we inject them into the group karate does i show before a lot of go to the brain
00:14:10
this is three days later no more cells pretty much but the
00:14:15
effect has been shown multiple times in power for immune modulation
00:14:19
uh so here this is traumatic brain injury different setting but they show the facts on display in they
00:14:25
showed effect on pro inflammatory cider kinds and and infantry side of kinds spleen size it's been way
00:14:31
so just by injecting here missing timeless themselves in the periphery there were able to demonstrate changes in
00:14:37
the periphery immune system that eventually led for instance
00:14:41
to recovery of blood brain barrier a permeability
00:14:45
so modulation of the performing an immune system i think might just
00:14:49
be as important as model lighting things in the brain
00:14:53
and finally when you look at the gene expression in the brain these
00:14:58
couple tells that going to the brain cannot really changed the whole
00:15:02
gene expression in the brain so here we have different
00:15:05
differential gene expression with or without cell injection
00:15:09
three days after treatment and take days as to treatment and if if we try to
00:15:14
group so this is from right brain come origin it's if we start grouping
00:15:18
these different pathways you see that we impact a lot of different pass
00:15:23
play cell proliferation cell signalling inflammation and this is done by
00:15:28
injecting stem cell so it's not an integration it's traffic support in
00:15:32
moderation of the environment that's at least what i believe
00:15:36
so summarising these results and be published is a also back a few years
00:15:41
is we're trying to find out what woody stem cells secrete
00:15:45
the axles owns again we go back to the testicles
00:15:48
i also believe that the good thing about the stance as they
00:15:51
can actually interact with their environment so the physical says
00:15:54
more static the cells can change their physical content upon integration
00:15:59
in the micro environment and what is the interaction
00:16:02
with the resident brain cells up and treatment with the goal
00:16:05
to hopefully have regeneration very briefly the hard being quite
00:16:10
several clinical trials uh almost all phase one trial i think
00:16:15
the best published trial is from the joke group
00:16:19
and was docked accord spared yeah your first talk to court and that has shown a
00:16:24
again in a small uh a number of inference that injecting biblical cord blood
00:16:29
derive stem cells or one biblical cold bought a enrich eh
00:16:35
actually lead to a better outcome of the few
00:16:37
children uh in the group that had cell spa schooling versus uh the children that had cooling only
00:16:44
and very interesting i think there is an ongoing um multi centre study now uh in the us
00:16:50
um that was the over twenty sites that is looking at
00:16:53
h. i. u. uh children uh uh with injection
00:16:56
of from biblical cord stem cells i i will skip dollars i think interesting trials in the future
00:17:04
early new or protection maybe already immune modulation through stem cells
00:17:10
uh maybe stem cell therapy in the more chronic phase i think
00:17:14
uh it d. and imagination is uh open a for discussion
00:17:19
am we have a few future things that we're investigating we're trying to develop by marcus from your
00:17:24
genesis there's no by the market from your bonuses how can be controlled what we do
00:17:29
so we can actually measure some factors into several spinal fluid a preclinical but we have
00:17:35
uh uh some clinical results uh that should be published soon uh on this topic
00:17:40
i'm not more cell cell interaction uh using new technologies like by printing and seeing
00:17:45
and finding out what factors actually influence the difference else clinical trials maybe
00:17:52
so summarising forty and i think for didn't c. n. s.
00:17:55
for the central nervous system we have have historically three
00:17:59
different approaches one being stimulation of indulgence repaired and i
00:18:04
believe today this is the most important we have
00:18:08
modulation and all of a d. uh immune system
00:18:12
by system excel infiltration i think this is
00:18:15
the first or the second most important i think this one cell
00:18:19
replacement is getting more uh uh in the back fire
00:18:23
i think there might be some indications for actual cell replacement
00:18:26
let's think about parkinson's in adults spinal cord injury
00:18:30
but at least in the neural net to field i think this is not the way we should think about
00:18:36
so finally i hope i was able to show you some evidence or some
00:18:40
data i add to a supported the idea of white matter regeneration
00:18:46
uh with modulation of political denver genesis and microbial activation
00:18:51
they're obviously there's many sources of cells that as we've heard before on
00:18:55
biblical cord worked where wardens generally bone marrow derives neural stem cells
00:19:00
i i don't think we know today which is the best there is several
00:19:03
options and maybe the options will have to be adapted to disease
00:19:08
apollo 'cause of obviously has the advantage of the ethical concerns uh and is uh uh is practical
00:19:14
hello janet a login a probably will have the advantage of scale ability if
00:19:18
we want to actually have it like a drug or be able to
00:19:22
uh uh develop it in a broader part of the work don't forget about
00:19:26
seventy or genesis is maybe it finishes at forty but probably continues
00:19:31
uh uh so keep exercising and uh i thank my funding
00:19:35
sources collaborators uh uh locally
00:19:38
and internationally thanks how
00:19:47
oh thank you ruffle forty so fascinating insights are there questions
00:19:52
from the audience it's so please use a microphone
00:19:58
overwhelmed her i have one question you you mentioned the uh the plot brain barrio once
00:20:06
um these inflammation necessary that the sales actually can go to the brain at all
00:20:13
uh it's it's a good question i think that inflammation and and i'm
00:20:18
not saying whether it's uh uh you know detrimental or helping
00:20:23
but yes i think eh it needs the op regulation of surface edition molecules
00:20:29
and you need expression of uh of of chemo kind soaking
00:20:32
wet track molecules so we get some studies where we
00:20:36
if the blocked let's say if you can as an additional the q. b. we blocked in the holes
00:20:41
or we blocked or eliminated the receptor on the cell
00:20:46
and you actually eliminate holding to the brain or we used a
00:20:50
a cells from transatlantic animals not expressing chemo kind we sectors
00:20:55
a if we eliminate or if we harvested from use transcending animals that do not have the chemo kind receptor
00:21:01
specific conference if you want to show two different ones you will actually abolish holding
00:21:06
so yes in a sense the broadband brain barrier itself i don't know if that's the crucial thing
00:21:11
but you do need to e. q. more traction on it you should capacity and aluminium uh
00:21:18
thank you very much already thirty questions
00:21:24
again these use microphone and very much for this very and interesting and fascinating talk of it and
00:21:30
she showed up and you can check to stem cells into detail braindead homing
00:21:34
would be normally what's the lines in the brain why is that
00:21:38
so what we found and again i am and i'm talking about the neural stem cells but there is a as many examples
00:21:44
for the other type of cells am that along serves as a filter and is like the first or gonna go through
00:21:51
if we look at the tape so we took out all the organs and you can too x. d.
00:21:54
will buy them lessons imaging don't you find the because proportioned along because it's the first pass
00:22:00
really hard back into the long but you do then fine cells in the spleen into lever and in the got and you do
00:22:06
find a few cells in the brain it's not that involves cells will actually go out but it's not the first pass so
00:22:13
income in in in contrast to this if we inject into the carotid artery
00:22:17
and you know coming from the at all stroke initially is uh when i started doing a experiments are so well
00:22:24
every patient has a stroll gets a catheter in for that from what i says so why not actually inject
00:22:29
this as what catherine forty really and that's where we see uh the the best homing to the right
00:22:36
if this is crucial i i leave it open for now and so if you imagine
00:22:40
a baby with a lot straight i th where would you normally think is your
00:22:45
best access to those so there has been studies trying intro
00:22:49
ventricular uh so directly to the c. s. s.
00:22:52
i i'm not convinced i actually still think intravenous introduces a good point because
00:22:58
again i believe in the power for the new modulation that has a big effect on the brain
00:23:02
and we have many examples from a projected an adult
00:23:06
literature eh at that there is big interactions i
00:23:09
think i. v. is the most practical and the
00:23:13
the biggest access to powerful peripherally remote location
00:23:19
okay thank you very much i'd like to close the session thank you everybody and i think we
00:23:25
or backing here at four o'clock sharp thirty five minutes more mature says five minutes more
Conference Program
Welcome words
Mathias Nelle, Bern
Jan. 16, 2018 · 9:36 a.m.
458 views
Personalised prediction of weight changes in the first week of life
Severin Kasser, UKBB
Jan. 16, 2018 · 9:41 a.m.
702 views
Q&A : Personalised prediction of weight changes in the first week of life
Severin Kasser, UKBB
Jan. 16, 2018 · 9:46 a.m.
397 views
Neurofilament serum levels as biomarker of neuronal injury in very preterm born infants
Antoinette Depoorter, PhD Candidate
Jan. 16, 2018 · 9:49 a.m.
339 views
Neonatal red blood cell (RBC) transfusion practices in Switzerland
L. Gosztonyi, C. Rüegger, R. Arlettaz, Neonatology USZ
Jan. 16, 2018 · 9:58 a.m.
317 views
Postnatal MR-Imaging and ADC Measures in congenital Cytomegalo-virus infection provide an added diagnostic value in characterizing white matter disease
L. Barrielle
Jan. 16, 2018 · 10:07 a.m.
111 views
Is intensity of perinatal care associated with increased neurodevelopmental impairment?
Giancarlo Natalucci, Swiss Neonatal Network and Follow-up Group
Jan. 16, 2018 · 10:15 a.m.
422 views
NEO (Neonatal Esophageal Observation) Tube - A feeding tube with monitoring function
Patrizia Simmen, Department of Neonatology, University of Basel Children's Hospital
Jan. 16, 2018 · 10:25 a.m.
572 views
Less invasive surfactant Application - Pro
Angela Kribs, Köln (DE)
Jan. 16, 2018 · 11:33 a.m.
1022 views
Less invasive surfactant Application - Contra
Sven Schulzke, Basel
Jan. 16, 2018 · 11:51 a.m.
1136 views
Q&A - Less invasive surfactant Application
Panel
Jan. 16, 2018 · 12:14 p.m.
316 views
Stem cells and birth
Martin Müller, Bern
Jan. 16, 2018 · 2:32 p.m.
677 views
Stem cells and white matter disease
Raphael Guzman, Basel
Jan. 16, 2018 · 3:16 p.m.
781 views
Protect the neurons: The challenge of the neonatologist and the researcher
Anita Truttmann, Service de Néonatologie, CHUV
Jan. 16, 2018 · 4:12 p.m.
541 views