imagine a day when a small piece of skin
or a few milliliters of blood could
dramatically change how scientists study
and understand the human condition
imagine a paradigm shifting resource
that could unlock the mysteries of aging
and development and provide previously
unattainable insights into the
foundational mechanisms that cause
disease imagine that that same starting
material could also provide a
therapeutic solution to a wide variety
of diseases that affect the human
population the reality is that this is
not some intangible future scientists
throughout an international research
community have been rapidly developing
the techniques needed to generate and
utilize patient specific stem cells for
well over a decade stem cells that have
the power to drive disease research and
therapeutic discovery very early in
human development there’s an incredibly
unique stem cell that is poised to
develop or differentiate into all the
unique cell types in the human body stem
cell biologists describe this unique
developmental state as pluripotency
through the process of differentiation
pluripotent stem cells ultimately give
rise to the diverse cell types that
comprised tissues tissues that make up
organs organs that interact in organ
systems and organ systems that
ultimately result in the biological
complexity that is us for the longest
time the predominating thought in the
scientific world was that this
developmental process only happens in
one direction essentially as stem cells
are exposed to small chemical messengers
they commit to a specific
developmental path and cannot revert
back to an earlier state imagine stem
cell as a ball at the top of a large and
undulating Hill as that ball is nudged
from its perch it rolls downhill
hitting key developmental transition
points along the way eventually the ball
comes to rest at the bottom of the hill
never to return to the top to repeat the
ride back down in 2006 a small group of
Japanese scientists led by Shinya
Yamanaka shocked the biological world by
turning this notion of one way human
development on its head through the
simple introduction of four key genes
Yamanaka and colleagues showed that you
could reverse a permanently developed
cell all the way back to the earliest
stages of development for the first time
they permanently developed permanently
mature permanently differentiated cell
was reprogrammed all the way back to the
pluripotent state Yamanaka named these
cells induced pluripotent stem cells or
I P SC s IPS CS have since
revolutionized the way scientists study
and understand the human condition and
have also provided a specialized sources
cells to treat disease for this
groundbreaking discovery Yamanaka was
awarded the 2012 Nobel Prize in medicine
so what does this reprogramming process
look like at first glance the routine of
generating induced pluripotent stem
cells from skin and blood is relatively
straightforward first donated biopsy
materials are processed to isolate the
cells of interest for example a small
piece of your skin could be broken apart
with enzymes into individual cells the
four key genes are then introduced and
cells are grown in specialized
conditions to help help them transition
towards the pluripotent state
after approximately three to four weeks
stem cells start to emerge as small
circular cell structures called colonies
colonies are then manually isolated
rigorously tested to ensure quality and
finally they’re frozen and banked after
two to three months of work involving
manual hands-on techniques we are left
with a small seemingly insignificant
vial of cells but as this material
originated from an individual with a
unique genetic background and these
cells have the power to differentiate
into any subtype in the human body we
are actually left with an incredibly
powerful tool to study disease to model
disease in a dish in a nutshell all of
the cells in your body have the exact
same genetic information if I were to
take a small piece of your skin and
reprogram it to induced pluripotent stem
cells the resulting IPS CS would retain
all the genetic information that makes
you unique
if those stem cells were then
differentiated into neurons heart muscle
or any other cell type the final soap
product would also retain the same
genetic information as the skin cells we
started with if we imagine this in the
context of an individual with a
diagnosed disease the power of this
technology becomes clear the induced
pluripotent stem cells are generated
from a patient that has Alzheimer’s
disease and then differentiated into
neurons we would be left with a dish
full of neurons that have the genetic
characteristics associated with
Alzheimer’s disease we would be left
with a dish full of neurons that behaves
like Alzheimer’s disease neurons
fantastic example of early work and the
disease modeling field comes from the
lab of rusty gage here at the Salk
Institute in 2011 publication gage lab
researchers showed that when induced
pluripotent stem cells were generated
from page
with schizophrenia and then
differentiate it into neurons the
resulting neural networks lacked the
complex cell to cell connections seen in
neurons differentiated from healthy
cells when those exact same
schizophrenic neurons were treated with
a commonly used fda-approved
antipsychotic researchers observed that
those cell to cell connections can be
rescued back to levels seen in healthy
cells this disease modeling approach is
by no means limited to schizophrenia
researchers here at the Salk Institute
have utilized patient specific stem
cells to study a wide variety of
diseases including Alzheimer’s
Parkinson’s multiple sclerosis autism
depression haemophilia cystic fibrosis
diabetes and more over the last decade
the routine of developing induced
pluripotent stem cells from skin and
blood has been well-established current
protocols are fairly robust allowing
most labs experienced with cell culture
techniques the ability to reprogram a
handful of patient cells with limited
difficulty things get interesting
however when six patients turns into 50
100 or 200 as with most tasks scale
changes everything
much like grandma’s secret cookie recipe
those delicious oatmeal chocolate
morsels are never quite the same when we
try a double batch as we move towards
doing more becomes incredibly difficult
to maintain a high quality product with
the power of induced pluripotent stem
cells becoming widely known the demand
for these specialized cells makes it
incredibly difficult for individual labs
to keep up this is exactly where core
facilities come in core facilities are
specialized resource centers built into
modern research institutes that allow
for the development and dissemination of
specialized techniques and technologies
here at the Salk Institute we have 13
such core facilities that provide access
to everything from the advanced imaging
technologies that allow researchers to
peer into the depths of cells with
mind-boggling clarity to the
next-generation sequencing technologies
that allow for unlocking the mysteries
of the genetic code we also have the
facility that I call home our stem cell
core facility where we focus on
providing human stem cell models
primarily to researchers here at the
Salk but also a larger local national
and international community in 2012 the
stem cell core was presented with an
opportunity to generate induced
pluripotent stem cells from over 200
individuals through a collaboration with
researchers here at Sauk and UC San
Diego armed with an intimate hands-on
knowledge of the reprogramming process
we were able to identify key transition
points and bottlenecks and the
reprogramming workflow allowing us to
break a complicated three-month process
down into individual functional steps
that patient cells could be staggered
through in small manageable groups a
process that enabled a team of
researchers to generate induced
pluripotent stem cells from over 222
individuals ranging from the ages of 9
to 88 and encompassing 41 distinct
family groups at the center of this
induced pluripotent stem cell collection
there are 39 individuals with diagnosed
cardiac disease and in many cases
representation from the parents siblings
and children of these individuals
ultimately this resource provides the
scale and variation needed to connect
small genetic changes to actual cellular
and molecular dysfunction that can be
observed when stem cells are
differentiated into medically relevant
cell types like the beating muscle cells
of
the heart 100% of these stem cell lines
have been shared with a world-leading
stem cell banking facility and are
immediately available to an
international cardiac disease and
broader research community is the
reprogramming process still
time-consuming yes is the process still
hands-on absolutely it is but with a
little bit of core ingenuity and a
dedicated and experienced staff we have
developed a process that works just as
well for 800 as it does for 8 beyond its
use of scale stem cell cores also play a
crucial role in pushing the boundaries
of the field by helping to develop new
and novel applications for stem cell
models a fantastic example of this is
organoid technologies traditionally stem
cell modeling involved growing cells
most often a single cell type on a flat
two-dimensional surface while this
approach has been incredibly fruitful in
expanding our understanding of disease
it never truly captured the complexity
of human biology and therefore has
limited our opportunity for discovering
while a dish full of just neurons could
tell us a lot about Alzheimer’s disease
a small highly organized cluster of
cells that more accurately captured that
the layered complexity of the human
brain could tell us a great deal more
scientists throughout the stem-cell
research community have been well aware
of this limitation and have been working
to develop protocols to generate these
3d clusters of cells that mimic organs
and also implement them into new and
novel disease modeling approaches here
at the Salk Institute researchers have
made groundbreaking discoveries in this
arena with protocols to develop both
kidney and brain organoids
and the stem cell core were actively
investigating ways to improve the
efficiency and variability of the
it’s all inspiring to consider the last
decade of induced pluripotent stem cell
research a fledgling technique to
generate patient specific stem cells has
grown into a highly robust and
reproducible technology allowing for the
development of thousands upon thousands
of unique patient specific stem cell
lines worldwide through the power of
scale large and well characterized
collections of induced pluripotent stem
cells are allowing researchers to
connect small genetic variations to
actual mechanisms that cause disease the
field has also started to push
traditional two-dimensional disease
modeling approaches into 3d organoids
that more accurately capture the
complexity of human biology where will
this exciting technology take us next
well well we’ll fully automated
reprogramming systems create a highly
efficient production process that makes
IPS cell therapies as routine as
prescription medicine will organoids
make the leap toward actual organs
providing an opportunity for rejection
free transplantation well large widely
available banks of induced pluripotent
stem cells generated from super donors
end up taking the personal out of
personalized cell therapies while the
future is not crystal clear what is
clear is that induced pluripotent stem
cell technologies represent a critical
tool for the development of advanced
therapies and with stem cell core
facilities driving efficiency and
innovation the possibilities are
limitless thank you [Applause]
or a few milliliters of blood could
dramatically change how scientists study
and understand the human condition
imagine a paradigm shifting resource
that could unlock the mysteries of aging
and development and provide previously
unattainable insights into the
foundational mechanisms that cause
disease imagine that that same starting
material could also provide a
therapeutic solution to a wide variety
of diseases that affect the human
population the reality is that this is
not some intangible future scientists
throughout an international research
community have been rapidly developing
the techniques needed to generate and
utilize patient specific stem cells for
well over a decade stem cells that have
the power to drive disease research and
therapeutic discovery very early in
human development there’s an incredibly
unique stem cell that is poised to
develop or differentiate into all the
unique cell types in the human body stem
cell biologists describe this unique
developmental state as pluripotency
through the process of differentiation
pluripotent stem cells ultimately give
rise to the diverse cell types that
comprised tissues tissues that make up
organs organs that interact in organ
systems and organ systems that
ultimately result in the biological
complexity that is us for the longest
time the predominating thought in the
scientific world was that this
developmental process only happens in
one direction essentially as stem cells
are exposed to small chemical messengers
they commit to a specific
developmental path and cannot revert
back to an earlier state imagine stem
cell as a ball at the top of a large and
undulating Hill as that ball is nudged
from its perch it rolls downhill
hitting key developmental transition
points along the way eventually the ball
comes to rest at the bottom of the hill
never to return to the top to repeat the
ride back down in 2006 a small group of
Japanese scientists led by Shinya
Yamanaka shocked the biological world by
turning this notion of one way human
development on its head through the
simple introduction of four key genes
Yamanaka and colleagues showed that you
could reverse a permanently developed
cell all the way back to the earliest
stages of development for the first time
they permanently developed permanently
mature permanently differentiated cell
was reprogrammed all the way back to the
pluripotent state Yamanaka named these
cells induced pluripotent stem cells or
I P SC s IPS CS have since
revolutionized the way scientists study
and understand the human condition and
have also provided a specialized sources
cells to treat disease for this
groundbreaking discovery Yamanaka was
awarded the 2012 Nobel Prize in medicine
so what does this reprogramming process
look like at first glance the routine of
generating induced pluripotent stem
cells from skin and blood is relatively
straightforward first donated biopsy
materials are processed to isolate the
cells of interest for example a small
piece of your skin could be broken apart
with enzymes into individual cells the
four key genes are then introduced and
cells are grown in specialized
conditions to help help them transition
towards the pluripotent state
after approximately three to four weeks
stem cells start to emerge as small
circular cell structures called colonies
colonies are then manually isolated
rigorously tested to ensure quality and
finally they’re frozen and banked after
two to three months of work involving
manual hands-on techniques we are left
with a small seemingly insignificant
vial of cells but as this material
originated from an individual with a
unique genetic background and these
cells have the power to differentiate
into any subtype in the human body we
are actually left with an incredibly
powerful tool to study disease to model
disease in a dish in a nutshell all of
the cells in your body have the exact
same genetic information if I were to
take a small piece of your skin and
reprogram it to induced pluripotent stem
cells the resulting IPS CS would retain
all the genetic information that makes
you unique
if those stem cells were then
differentiated into neurons heart muscle
or any other cell type the final soap
product would also retain the same
genetic information as the skin cells we
started with if we imagine this in the
context of an individual with a
diagnosed disease the power of this
technology becomes clear the induced
pluripotent stem cells are generated
from a patient that has Alzheimer’s
disease and then differentiated into
neurons we would be left with a dish
full of neurons that have the genetic
characteristics associated with
Alzheimer’s disease we would be left
with a dish full of neurons that behaves
like Alzheimer’s disease neurons
fantastic example of early work and the
disease modeling field comes from the
lab of rusty gage here at the Salk
Institute in 2011 publication gage lab
researchers showed that when induced
pluripotent stem cells were generated
from page
with schizophrenia and then
differentiate it into neurons the
resulting neural networks lacked the
complex cell to cell connections seen in
neurons differentiated from healthy
cells when those exact same
schizophrenic neurons were treated with
a commonly used fda-approved
antipsychotic researchers observed that
those cell to cell connections can be
rescued back to levels seen in healthy
cells this disease modeling approach is
by no means limited to schizophrenia
researchers here at the Salk Institute
have utilized patient specific stem
cells to study a wide variety of
diseases including Alzheimer’s
Parkinson’s multiple sclerosis autism
depression haemophilia cystic fibrosis
diabetes and more over the last decade
the routine of developing induced
pluripotent stem cells from skin and
blood has been well-established current
protocols are fairly robust allowing
most labs experienced with cell culture
techniques the ability to reprogram a
handful of patient cells with limited
difficulty things get interesting
however when six patients turns into 50
100 or 200 as with most tasks scale
changes everything
much like grandma’s secret cookie recipe
those delicious oatmeal chocolate
morsels are never quite the same when we
try a double batch as we move towards
doing more becomes incredibly difficult
to maintain a high quality product with
the power of induced pluripotent stem
cells becoming widely known the demand
for these specialized cells makes it
incredibly difficult for individual labs
to keep up this is exactly where core
facilities come in core facilities are
specialized resource centers built into
modern research institutes that allow
for the development and dissemination of
specialized techniques and technologies
here at the Salk Institute we have 13
such core facilities that provide access
to everything from the advanced imaging
technologies that allow researchers to
peer into the depths of cells with
mind-boggling clarity to the
next-generation sequencing technologies
that allow for unlocking the mysteries
of the genetic code we also have the
facility that I call home our stem cell
core facility where we focus on
providing human stem cell models
primarily to researchers here at the
Salk but also a larger local national
and international community in 2012 the
stem cell core was presented with an
opportunity to generate induced
pluripotent stem cells from over 200
individuals through a collaboration with
researchers here at Sauk and UC San
Diego armed with an intimate hands-on
knowledge of the reprogramming process
we were able to identify key transition
points and bottlenecks and the
reprogramming workflow allowing us to
break a complicated three-month process
down into individual functional steps
that patient cells could be staggered
through in small manageable groups a
process that enabled a team of
researchers to generate induced
pluripotent stem cells from over 222
individuals ranging from the ages of 9
to 88 and encompassing 41 distinct
family groups at the center of this
induced pluripotent stem cell collection
there are 39 individuals with diagnosed
cardiac disease and in many cases
representation from the parents siblings
and children of these individuals
ultimately this resource provides the
scale and variation needed to connect
small genetic changes to actual cellular
and molecular dysfunction that can be
observed when stem cells are
differentiated into medically relevant
cell types like the beating muscle cells
of
the heart 100% of these stem cell lines
have been shared with a world-leading
stem cell banking facility and are
immediately available to an
international cardiac disease and
broader research community is the
reprogramming process still
time-consuming yes is the process still
hands-on absolutely it is but with a
little bit of core ingenuity and a
dedicated and experienced staff we have
developed a process that works just as
well for 800 as it does for 8 beyond its
use of scale stem cell cores also play a
crucial role in pushing the boundaries
of the field by helping to develop new
and novel applications for stem cell
models a fantastic example of this is
organoid technologies traditionally stem
cell modeling involved growing cells
most often a single cell type on a flat
two-dimensional surface while this
approach has been incredibly fruitful in
expanding our understanding of disease
it never truly captured the complexity
of human biology and therefore has
limited our opportunity for discovering
while a dish full of just neurons could
tell us a lot about Alzheimer’s disease
a small highly organized cluster of
cells that more accurately captured that
the layered complexity of the human
brain could tell us a great deal more
scientists throughout the stem-cell
research community have been well aware
of this limitation and have been working
to develop protocols to generate these
3d clusters of cells that mimic organs
and also implement them into new and
novel disease modeling approaches here
at the Salk Institute researchers have
made groundbreaking discoveries in this
arena with protocols to develop both
kidney and brain organoids
and the stem cell core were actively
investigating ways to improve the
efficiency and variability of the
it’s all inspiring to consider the last
decade of induced pluripotent stem cell
research a fledgling technique to
generate patient specific stem cells has
grown into a highly robust and
reproducible technology allowing for the
development of thousands upon thousands
of unique patient specific stem cell
lines worldwide through the power of
scale large and well characterized
collections of induced pluripotent stem
cells are allowing researchers to
connect small genetic variations to
actual mechanisms that cause disease the
field has also started to push
traditional two-dimensional disease
modeling approaches into 3d organoids
that more accurately capture the
complexity of human biology where will
this exciting technology take us next
well well we’ll fully automated
reprogramming systems create a highly
efficient production process that makes
IPS cell therapies as routine as
prescription medicine will organoids
make the leap toward actual organs
providing an opportunity for rejection
free transplantation well large widely
available banks of induced pluripotent
stem cells generated from super donors
end up taking the personal out of
personalized cell therapies while the
future is not crystal clear what is
clear is that induced pluripotent stem
cell technologies represent a critical
tool for the development of advanced
therapies and with stem cell core
facilities driving efficiency and
innovation the possibilities are
limitless thank you [Applause]
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