one of the most intriguing uses of stem
cells can be found in the field of
regeneration whether the goal is to
regenerate damaged heart or nerve cells
or to regenerate an entire limb a
similar process must occur a damaged
tissue must rewind development calling
on cells that can reverse their
differentiation or rallying reservoirs
of stem cells that can generate both
differentiated cells and more stem cells
humans can regenerate certain parts of
the body wound healing is a poorer
cousin of regeneration but the human
liver for example can regenerate an
entire piece if it has been lost through
damage or surgery other vertebrates are
more proficient than mammals at
regeneration some lizards and
salamanders regenerate lost tails and
salamanders can regenerate entire limbs
however the organism with one of the
most incredible abilities to regenerate
is the planarian this worms regenerative
capabilities have been known for
hundreds of years and today modern
molecular biology techniques are turning
this old favorite into a powerful new
model for understanding the potential of
stem cells
planarian are free-living flatworms and
are related to parasitic flatworms like
the liver fluke and the tapeworm they
are found throughout the world in wet
environments they range in size from 3
to 12 millimeters and are scavengers
feeding on the decaying remains of
animals and plants dr. Alejandro Sanchez
Alvarado and HHMI investigator at the
University of Utah describe some of the
preneur Ian's physiology linear as you
write their name from the fact that
they're fairly flat a Planum mean flat
and hence planarian and and the reason
why they're interesting is because these
are perhaps the simplest organisms that
display is centralized a nervous system
so the central nervous system is
composed of two lobes that look like a
horseshoe shape around this area right
here and those two are connected to
ventral cores that send projections all
the way down to the very tip of the
animal and this is how the the brain
basically controls the motion and
musculature of these of these animals
this dark grey area right here is part
of the gastrovascular system this little
thing right here is a muscular pharynx
which actually comes out from the
ventral surface from the belly of the
animal out and is used to impale
literally impale food and suck it back
in now a planarian are funny because
they don't have a mouth so they only
have a single opening to their body and
it's through these pharynx so the food
enters through the pharynx it is
digested and whatever is not digested
and it's not dumped into the rest of the
animal comes back out through the same
pharynx so it's an organ that serves two
functions these two cartoon looking
cocci eyes right here actually are the
photoreceptors of these of these
planarians were also known as eye spots
and what these eye spots can do is
detect light and planarians are done
like light their photo tactically
negative so whenever they see light
they'll just run away from the light and
they'll hide somewhere and this is
perhaps you know the prototypic other
Darwinian eye which consists of a light
sensing organ and a pigment cup organ
that allows for the light to be handled
by the organism but what makes a
planarian so exceptional at regeneration
is its ability to rapidly grow even very
small body pieces into completely formed
worms
unlike the cells of most animals most of
the cells in a planarian body can act
like stem cells if you cut a planarian
in half between its head and tail the
tail half grows a head and the head half
grows a tail if you cut it lengthwise
the two halves grow new second halves
you can even bisect just the head
between the two I like photoreceptors
and you will end up with a worm with two
heads this process can be taken to
incredible extremes dr. Sanchez
Alvarado describes the planarian ability
to regenerate so you can take a
planarian and slice it into eight
fragments okay and each fragment will go
on and regenerate a complete animal that
will be like saying that you know you
can cut your ear off and then a new you
will arise from that ear where
planarians can do that we can but
learners can do that more again in 1898
demonstrated that you can take a
fragment that's one 279 the size of the
original animal and that tiny little
fragment for the flank of the animal
will be capable of restoring all of the
missing parts and produce a complete and
properly shaped organism and it does
this in about a week or so and so that
just gives you an idea of how plastic
these animals are Thomas Hunt Morgan
investigated the planarians regenerative
powers at the turn of the 20th century
even before Morgan Charles Darwin wrote
about planarian he found during his
voyage on the Beagle describing their
abilities and illustrating their Anatomy
what new information has modern-day
biology been able to uncover about
planarian stem cells and regeneration
and what do these findings tell us about
the human capacity for regeneration at
the University of Utah the Sanchez
Alvarado lab is using today's molecular
biology tools to uncover the secrets
behind the planarian remarkable
abilities they use a particular type of
planarian Schmidty a Mediterranea in
their research auto google halfa a
graduate student in the sanchez alvarado
lab explains the advantages of using
planarian to study stem cells but I
didn't feel like the mammalian system is
ready to tell us a lot I felt like a lot
of the basic knowledge that we need to
know in order to ask the right questions
about stem cells needed to be discovered
in a much simpler organism so although
the mouse work is very very interesting
I thought studying it in a much simpler
organism will be much more interesting
and that's how I got turned on to
studying stem cell biology in planaria
experiments using RNA interference or
RNAi I were designed to identify the
genes involved in the planarians
neoblasts the stem cell-like cells that
migrate to areas of damage and allow the
worm to regrow the missing parts of its
body
the RNA I experiments identified 240
genes involved in a planarian
regeneration including one coding for a
protein called Smedley that is similar
to proteins found in fruit fly stem
cells and during the process of human
sperm maturation these molecules met we
receives his name because it's a homolog
of a molecule that was discovered in
drosophila called peewee and peewee is a
molecule that was identifying herself as
being responsible for the maintenance of
the stem cells in the gonads of of the
female fly we were expecting peewee to
actually play a role in the in
regulating the maintenance of the stem
cells that are found in the body plan of
planarians and so the original phenotype
the defect that we uncover by
eliminating this genius in dose and the
RNA said that that was the case because
the animals look a lot like what
irritated animals look like and
irritated animals basically have no stem
cells because the stem cells are the
only cells that divide in planarian so
you subject them to large doses of
irradiation like you would do for cancer
for example all the dividing cells are
eliminated and there's no stem cells to
produce new daughter cells to go in and
replace these dying cells and the animal
dies and it does in a very specific way
the head begins to resort back and the
body begins to assume a ventral curling
so the animal now looks almost like a
taco shell when we silence piggy with
RNA i we got exactly the same phenotype
a regression of the head and this
curling phenotype so we thought aha when
we look at these animals in detail all
those stem cells are going to be gone
because we're essentially getting the
same defect what we were surprised
because when we went and look at these
animals we realized that the stem cells
were there they were happy the stem
cells were actually responding to Tisha
turnover so they were producing division
progeny and so the message there was to
us that pea would not only have a
function in the maintenance of stem
cells but it actually had a function in
regulating the function of daughter
cells
so you're causing a defect early on in
the life history even before that that
cell is born that when the cell Anna is
now born is supposed to go on and
differentiate it cannot and then it
fails and they undergo apoptosis most
likely and then it dies so the lesson is
actually quite profound for us because
it tells us that this molecule Pewee is
actually doing something to the genome
of the stem cell that will determine
whether or not the daughter
so we'll be functional but how much of
this knowledge will be relevant to human
stem cells I think the main thing that
could be applied to human invertebrate
biology based on what we're learning in
the planaria right now is identification
of genes so by identifying these genes
that are involved in planarian
regeneration hopefully we can understand
their function in humans these are genes
that are promoting regeneration in
planaria it may be possible somewhere
farther down the line to turn these
genes on pharmacologically and they may
have some effect in vertebrates
multicellularity is been around for
about 600 million years so the history
of life on this planet is unicellular
it's just all single cells so it took
you know 3 and 1/2 million years only
600 million years ago multicellularity
emerge and one of the fundamental
attributes I think of multicellularity
is the maintenance or segregation of the
germline into stem cells to repair
tissue which we damaged all the time
even Drosophila has now stem cells in
its gut which is absolutely required to
keep nutrition to the stem cells in the
gonads such that the animal can
reproduce so I think all these processes
at some way we're going to be conserving
by studying planarians we might be able
to form that biology by extension
understand our own biology a little bit
better than we do today
you