I'm Todd McDevitt I'm an assistant
professor in the department of

biomedical engineering Georgia Tech and
Emory University and

I'm going to introduce some of
the work that my lab is doing

with regards to engineering
stem cell technologies.

So what is the need for
stem cell engineering summarized here

is kind of snaps of the field in
which case we see that basic science

has greatly advanced our ability to
understand how to derive expand and

propagate various types of stem cells and
also we have an increasing amount of

information about how to differentiate the
cells have divided different cell types

and with this new knowledge base it lends
itself to a variety of different types of

applications such as in
vitro diagnostics and

perhaps drug visit discovery in
pharmaceutical platforms and

another areas create tremendous interest
for the opticians themselves is that for

tissue repair in the in the realm
of regenerative medicine.

So how do we go from these
fundamental discoveries in

basic science of stem cell
biology to wards these athletes

these applications on the other
end of the transformer spectrum.

And the idea of this in the focus of my
laboratory is to address this very problem

which is to create sort of the engineering
based approaches that we can use to

translate the basic
science discoveries into

into commercially realizable and
viable applications.

Scryers three primary things one is
the ability to be able to control aspects

of the environments to which
stem cells are cultured in

introduced in order to control
the phenotype in their differentiation.

Another is to be able to earn another
important principles to be able to

develop technologies that are both
robust and inherently scalable so

that we can take discoveries made at the
bench top level and immediately translate

those into in a way that can be greatly
expand larger numbers of cells and

also to take into consideration the
formats of these cells which deliver will

configurations in which they may be
useful for some of these applications.

And so therefore our overall
goal is the anticipation that we

can translate the potential of stem
cells into innovative therapies and

future diagnostics.

So there's a variety of types of stem
cells starting with the perhaps most

primitive or most potent pluripotent stem
cells such as embryonic stem cells and

their capacity to differentiate into
a variety of different lineage restricted.

For genitor cell types.

Multi-posting stem cells comprising
ectoderm is a term and a term German ages

all the way down to variety even broader
variety of different types of magic cells.

And in recent years it's also been
demonstrated by never investigated is

that these errors which
largely predominately

were oriented moved in one direction from
these more primitive states these more

mature sematic cell States can
also be are somewhat reversible.

And this is launched the whole idea
about the reprogrammed reversibility of

cell state.

Art One of our main focus
in our laboratory is

at this first interface which is
how can we fish efficiently and

effectively direct
the differentiation of the cells

at different stages of development to
more defined and homogeneous populations.

A second.

Goal then is that having a hopefully
achieve attained or achieve this.

What are some of the types of by
a process by analytics that as we start

to produce different types of cell types
we can use to both greatly enhance and

scale the production of of cells and
cell derivatives.

But also be able to analyze these
in a nondestructive fashion.

And ultimately then as I said early on one
of our primary interest is in the area of

regenerative medicine and two areas with
this one is that the up patients in which

the cells themselves are clearly useful
for some type of rejoinder of cell

therapy but we're also interested in a
potentially alternative hypothesis or use

of the cells which is the characterization
and development of stem cell.

Dr biologics cases in which the cells
themselves actually can produce factors

that are useful for
regenerative applications.

So the summarizes the.

Three kind of primary focus areas within
our lab which is engineering the stem cell

environments largely in order to control
differentiation in the phenotype of

the cells stem cell as we move then
Towards Healing process some processing

and the analytical tools necessary
to enable this or are important and

this also then will put we think
potentially be able to be useful for

development attention in a silly or
non solar therapies from

molecular region of therapies from stem
cell sources as it which can also then

give us some insights into
the protectors of some cells produce and

the effects on morphogenesis
which feeds back as well.

Back into this the engineering
of the Stem Cell environments.

So we have this integrated framework upon
which a number of our projects are our

interfacing.

So to summarise just some of the areas
a few years back we embark on one project

for which we've been fortunate to receive
funding from National Science Foundation

and more recently from the National
Institutes of Health this work is is

based upon the idea of how can we begin to
integrate signals in a controlled manner

and be able to present morphogenetic
factors in particular in special

temporally controlled with tissue with
controlled spatial temporal presentation.

So depicted here is one idea of this
in which we could basically fabricate

biomaterials of various compositions.

Also in capsule a different factors but it
can be released from the interior of these

materials as well as from the some
of the surface moiety as they can be

either directly conjugated attached or
tethered.

And in the work that we published in
recent years we demonstrate that we can

fabricate for example literally degradable

microspheres we can in cat
incorporate these within three D.

stem cell aggregates referred to in
this case the number of bodies that we

can see die of the small molecule or
dye release that emanate out from these

particles with the same kinetics
of that of degradation and

then we use a small molecule such as
retinal Cassatt we actually see that we

get extremely homogeneous differentiation
of the population these cells.

And we've gone to characterize
the different phenotypic

states of these cells and
this is just our national for

a in proof of principle to
demonstrate how this might work.

One of the the things we then more
recently done in collaboration with

Peter's Asher's lab from University
of Toronto is also be able to

begin to use some additional micro
technologies that we enable us to

incorporate a wider array of different
types of potential delivery vehicles and

to do this in a manner in which we
can homogeneously present these in

large populations of the of
these cell aggregates and

even We've recently been able demonstrate
the potential for spatial control within

these terms laggards where we can actually
control different populations of particles

thereby delivering different signals
in a specially controlled manner.

More recent project that we are are
embarking upon also in collaboration with

this incorporation with our
glazes group here in Georgia Tech

is actually to be able to think about
how we can increase the throughput for

screening the temporal kinetics facts
of different types of mortgages

of some cell differentiation and one of
the ways in which we've vision doing this

is through the use of microfluidic
platforms which will enable us to not only

control the spatial presentation
of various types of mortgages and

hide at high density in close proximity.

But also be able to control the temporal
kinetics in which the different mortgages

are presented to the cells and

be able to then relate this back
to differentiate itself fate.

So the goal of this work in general is how
can we really be able to assess this this

huge expanse of experimental space and
come up with more systematic approach is

to be able to present differentiation
factor suit to cells in order more closely

control and understand the mechanisms
of regulating stem self a decision.

During the course of this work.

We also kind of came across some
additional types of primers that we

weren't necessarily expecting
to influence differentiation and

that's the picture here where we actually
in these initial studies where subjecting

our embryonic stem.

Cells in suspension to this simple orbital
culture system in our E.Q. readers

what we found was that we got a much more
homogeneous population of the overall

different cell aggregates We then went
on to discover that these this simple

change to the culture method actually had
significant differences it with regards

to differentiation of cells particularly
with regard to cardio my ascites which was

readily evident from some frontin is
contract activity as well as some

additional gene expression studies and
flow cytometry analysis that we performed.

This then prompt us to actually start to
begin to look even more systematically at

this to understand the perhaps
the role of Hydra Namath's and

how these might actually be able to affect
stem cell differentiation and so more

recently from Bart in this large study to
basically be able to try and characterize

this within this same system and the idea
behind this is that we can see that we can

reproduce only control populate
the size of the different aggregates in

a large population based format and
that murderous lead that we found is that

there are actually gene expression
differences in a number in a variety of

genes that are subjected to either
static or hide or dynamic conditions.

So what this suggests is that even so
simple subtle cues that may exist within

the system by reactor systems in
particular where mixed conditions

are introduced can actually also have
an effect on cells in addition to some of

the more for the bar chemical and other
types of biophysical morphogenetic or

more generic factors that have
been previously examined.

One of the the third area that we just
want to touch on is also our work then in

thinking about not just with the cells or
are turning into but

also at the same time.

What are these cells producing and

shown here is we see over time course we
see a number of morphological changes of

the guards to the phenotype of
the cells but we also see that for

example in the presence of mineral
is a mineral izing substrate as

a bit of glycerol phosphate that we can
actually see these cells have a capacity

as the undergo differentiation to actually
produce mineralized major cities.

This has really led us to kind of
start to think about what is perhaps

unique about the composition
of embryonic major cities or

or major cities derived from
pluripotent stem cells and

we've done a significant amount of work
to examine the the temporal kinetics

of gene expression that occur with
specific regard to actually matrix and

growth factors over the time course
of early bird body differentiation.

We've confirmed the presence and
the spatial distribution of

these molecules and
also going on to take a look at

some of the correlation with some of the
different phenotype the cell phenotypes

that we see regionally emerge with within
this these different masses of cells.

This is obviously it takes a tremendous
our work to understand the biology of

what's going on but one of the motivations
for this is then to begin to think about

how we might actually be able to decently
arise such environments in order to create

a template for some novel detail your eyes
materials that may be useful for good for

soft tissue repair and other types of
tissue regeneration applications and

so we've developed a number of
methods both using solvent based

methods combinations of per
realization agents and enzymes

examined the characteristics of the
residual major cities and also be able to

do this similar types of things with other
types of mechanical means and examine

the ability of these types of major
cities to support cellular repopulation.

We've also moving this along into more bio
activity studies to examine the response

of exogamous cell types through a
combination of in vitro such as migration

essays for some of these materials and
also some in view dermal

wound healing studies that we've been
conducting over the past several years.

The overall goal of this port part of
portion of our lab is really to try and

have a better understanding of the types
of molecules uncomment complex city

that exist within the biochemical
mill you that stem cells can produce

how it's related is a function
of differentiation of the cells.

Also to think more broadly about how
we might be able to use this type

of information to directly extract or

perhaps engineer new types of
regenerative their molecular therapies.

So just want to acknowledge and thank
the members of my lab all depicted here.

I also want to ban egg knowledge to
these group members as well as some of

the undergraduates who have worked with
us in a number of the lab that have

worked with us over the past five years
and especially want to thank all of my

collaborators both at Georgia Tech as
well as in the more global community that

I've had the fortune opportunity to work
with on a variety of these projects.

I also want to acknowledge and thank our
funding sources as I mentioned earlier

particularly the National Institutes
of Health and S.F.

an American Heart Association as well as
the Georgia Research Alliance Johnson and

Johnson and
some of the local agencies such as G.

Tech and the Parker Institute for
Bioengineering and bio science

as well as an opportunity granted last
year to be visiting scientists for

a short period time in the U.K.
that was made available by this U.K.

the U.S.
stem cell collaboration development work.

Thank you very much.