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Tissue Engineering
A.K.A. regenerative medicine
Lab tested, Vatican approved
In a nutshell
We Break.
Mike Tyson vs. Evander
Holyfield: Ear Bite
Marty McSorley of the
Bruins slashing Donald
Brashear of Vancover in
2000, McSorley was
suspended indefinitely
Even more serious: Heart
transplants, Kidney failure,
Liver disease, we need
parts replaced, regrown.
Still thousands die while waiting for a transplant,
and thousands more aren’t even on the list.
400 bil: ½ of
national
health care
bill goes to
patients with
organ failure,
or tissue loss
T. E. is the next wave
• Grow your own
tissue outside of
your body and use it
for later repair
– Burn victims use
skin grafts
• OR: implant Growth
Factors that tells
cells where to grow
• OR: planting a
scaffold seeded
with your own stem
cells into the body.
•Grass grows back, starfish arms grow
back, why not your amputated arm?
What areas of life science have
been affected by T.E.?
• Medical field
– Geriatrics
– Therapies
•
•
•
•
•
Anatomy
Cell science
Genetics
Evolution
Botany?
– Agriculture
• CAD/ engineering
• Pharmaceuticals
• Physics
Why evolution?
because this is technology that could
dramatically increase human life span
applications
• Tissue replacement
for
– Disease
– Trauma
– Congenital problems
• Battlefield wounds
• Transplantation
• Improve performance
How much would you pay for a super
star athlete’s body? Lance’s heart,
Tyson’s teeth,
Stephen Hawking Builds Robotic
Exoskeleton, from the onion
Time’s hottest jobs of the future
1. Tissue engineers
2. Gene programmers
3. Pharmers
4. Frankenfood monitors
5. Data miners
May 22nd 2000
Current therapies
1.
Autograft: very personal
recycling
–
–
2.
Unless you run out of
yourself to graft
Rejection isn’t a problem
Allografting
–
–
–
–
Allo: different
From another member of
same species
Most common
Skin, corneas, heart,
liver, kidney, bone
Speaking of Allo: Tasmanian
Devils have been hit by what’s
called an allograft transmissible
cancer, Devil Facial Tumor
Disease
Very weird
cancer
spreadable by
touch
Very Lethal
Current therapies
3. Xenografting
–
–
–
–
–
Taking tissue from another species
Easy supply, but ethical
considerations, & rejection
Started in 60’s with chimp kidneys
Potential for disease spreading, a
pigs immune to somethings, but
we are not
Lance Armstrong’s dog has a heart
valve made of bovine tissue
•
He’s a winner
6
Current
therapies
5
4
3
Series1
4. Man made stuff
– Artificial hearts,
valves, hips, and
breast implants.
– Problems: wear & tear,
need for replacement,
not organically
versatile.
– Depends on how you
view the speed of
technology.
2
1
0
1880
1900
1920
1940
1960
1980
2000
2020
Predict where the next number will be.
What is this a graph of?
T.E. will surpass these therapies
• Grow tissues outside the body
for later implantation
– Like skin
• Implanting devices that induce
the regeneration of tissue
– Like a trellis for ivy to grow up
– Get your growth factor on
• Stem Cell therapies
• Goal: Cheaper & better.
• Dare I say it? CHANGE THE
WORLD
So think for a minute…
• What areas of life science, besides
medical, or technology have been affected
by T.E.
• Agriculture, Biophysics, biomaterials,
computer modeling
Cells: T.E.’s raw materials
• Basic unit, but rarely
autonomous
– Too much
specialization
– use E.C. matrix
• Grouped together:
tissues
• Histology: Study of
tissues
To figure out how to restore/ replicate
tissue you’ve got to understand its
origin & development.
• 1998: Geron corp.
figures out how to
extend telomeres.
– We lose a little
telomere every time a
cell divides.
– Part of aging process
– Telomerase extends
them
• Hayflick limit: cells in
culture divide ~ 50
times, towards the
end they show signs
of aging
– Prevents cancer
Immortal cell lines
• Lobsters grow during the
course of their whole life.
(biggest 45 #’s, but size does
not = age)
• Theories exist that hydra
show no signs of aging
• The human liver can
regenerate from as little as
25%
• MRL mouse: regenerates
holes punched in ears without
scarring.
Regeneration in mammals
• The human liver can
regenerate from as
little as 25%
• Little kids can grow
back everything on
their fingertip before
the first knuckle
• MRL mouse:
regenerates holes
punched in ears
without scarring.
Tissue origins
• Embryonic cells
present
molecules on
their membranes
that aid in the
early organizing
process
– Ectoderm,
mesoderm,
endoderm
4 types of tissue
• Epithelial, connective,
muscle, nervous
• They’ve all got an E.C.
Matrix (ECM) around
them.
– Whether soft as in blood, to
hard as in bone
• Big question: How do the
cells know what to
become, how do they
know to stay that way?
– What about you, how did
you know where to fit in in
high school, did you stay
fitting in there?
• Remember every
somatic cell has
the set of
instructions for
every protein in
your body.
• Cells throw growth
factors back and
forth turning genes
on and off.
• Some cells are too
specialized, and
can’t go back. A
problem, but also
useful.
– Don’t want your CNS cells
getting the wrong idea
Your body works through extraordinary
teamwork
• A cell that is able to differentiate into
many cell types is known as
pluripotent
– Can’t grow into a totally new indiv.
Because they don’t make
extraembryonic structures like placenta
• A cell that is able to differentiate into
all cell types is known as totipotent.
– Can go full on into a new indiv. They
can make a placenta
– Amazing: plants are way easier to find
totipotent cells in
Beast boy can
turn into any
animal
You’ve got stem cells in you right
now
• Note: Progenitor cells: a term like
stem cells, but less restrictive
• Adults have stem cells in blood
marrow.
– They’re multipotent, but not pluripotent
– Might have suffered ravages of time,
sunlight, and toxins, that come with
aging
• There are also stem cells in
umbilical cords
• Embryonic stem cells = controversy
Bo is like a
pluripotent athlete.
•Hot research area: harvest embryonic
stem cells without destroying the embryo.
Short form: Know the argument
• Proponents
– They’re from embryos that are slated for destruction
anyway
– Great potential for good
– Superman was for it
• Only for embryoes that were
going to be discarded
• Opponents
– Destroys embryos
– Devalues worth of human
Proponents Argument in
depth
– Embryonic stem cells are more useful
– Utilitarian
• The benefits of stem cell research outweigh the
cost in terms of embryonic "life“
– human potential vs humanity
• The value of an embryo should not be placed on
par with the value of a child or adult
• Life starts with a heartbeat
– Ends justify the means
– Efficiency
• If an embryo is going to be destroyed anyway, isn't
it more efficient to make practical use of it?
• In Vitro Fertilization makes thousands of unusable
embryos
Opponents
arguments in
depth
– Embryos are lives
• Life starts at conception
• Note Roe v. Wade said life = viability, ability to
survive outside of womb, medical advancements
have pushed this back to 22 weeks. Could trend
continue?
– Exploring alternative therapeutic options
• We’ve studied adult stem cells longer and have
more therapies with them that with embryonic
– The potential is overstated
Legally
• In the U.S.
– Clinton would have been okay for studying
embryos left over from in vitro, but in the end
the law was: no research that results in
destruction of embryo.
– Bush said, its okay to study the cell lines that
already exist, just no destroying embryos.
– THIS IS JUST GOVERNMENT MONEY.
Private research is whatever dude.
– Lately congress has been pushing to get $ for
studying embryos.
Who’s where?
• Legal
• Sweden, Finland,
Belgium, Greece, the
United Kingdom,
Denmark, and the
Netherlands
• China, Japan, Korea,
Taiwan
• Israel, Iran
• Illegal
• Germany, Austria,
Ireland, Italy, and
Portugal.
• Most of middle east
• Africa, except S.
Africa
• S. America, except
Brazil
Bone T.E.
• We are full on in the middle of the
bone and joint decade.
• Quick show of hands, whose broken
a bone?
• Mayans were putting in shells
where teeth fell out, more than 1K
years ago.
• Bone likes to grow onto titanium,
which lasts a long time.
Scaffolds
• Allow cell attachment and migration
• Deliver and retain cells and biochemical
factors
• Enable diffusion of vital cell nutrients and
expressed products
• Exert certain mechanical and biological
influences to modify the behavior of the
cell phase
• Need a certain porosity, biodegradability,
• This animation of a
rotating Carbon nanotube
shows its 3D structure.
Carbon nanotubes are
among the numerous
candidates for tissue
engineering scaffolds
since they are
biocompatible, resistant to
biodegredation and can be
functionalized with
biomolecules.
• Questions how to get the
Growth hormones and cells
to the scaffold in the right
conc. At the right times.
• Note: this mouse didn’t grow
the ear, a scaffold was
placed in it, and the cells
grew around the scaffold.
A Heart valve grown in a dish
Bioreactors
• Systems that support
biologically active
environment
• Device for growing cells
• Lots of variables to
control
• NASA’s designing one to
see if microgravity is a
better environment to
grow tissuespeople never
get off this waiting list.
This lab-grown blood vessel
developed in the bioreactor just
as it would in the body
Cloning
• A “clone” is a copy of
something.
– Computers that mimic
IBMs are called “clones.”
– In genetics, a clone is a
genetic copy of another
organism.
• Clones occur naturally:
– Asexual breeding in plants
& lower animals
– Identical twins (triplets) in
higher animals
Lohan clones
History
of Cloning
• For centuries it has been
known that simple
animals – worms &
starfish – can be cloned
by cutting them in half.
• This doesn’t work for
higher animals!
• Part of the problem is cell
specialization:
– Nerve
– Bone
– Muscle, etc.
Cloning in the
20th Century
• We now realize that each
specialized cell has all the
genetic information, but
much of it is turned off.
• Problem – how to reset
the “program” so this
information is usable?
– Cloning of frogs successful
in 1950s
– Cloning of livestock from
fetal cells in 1970s
Dolly - 1996
• Clone from an adult
sheep cell by Scots
researchers under Ian
Wilmut
• Had only one success in
300 tries.
• Dolly grew to maturity,
and successfully had a
lamb by natural means in
1998.
• But Dolly seems to be
prematurely old.
Cloning since Dolly
• Cloning of this sort has now been done on
cattle, pigs and mice also.
• The success rate has improved
considerably.
• Cloning humans begins to show up in
science fiction in 1970s.
• This is now a realistic possibility.
Advantages of Cloning
• With an adult plant or animal, the breeder
knows what its traits are; this is not the
case with fetal cell cloning.
• Cloning allows making a genetically
identical copy of the desired plant or
animal.
Concerns re/ Cloning
• The success rate from adult animal cells is still
rather low.
• This would be unacceptable for cloning humans
in most societies.
• The evidence suggests that the clones which
survive are still not right.
• The genetic program has probably not been
completely reset.
• We still don’t understand what we are doing in
cloning from adult cells.
T.E. is interdisciplinary
• Science is highly
specialized
• A biophysicist,
pharmacist, and a
orthopedist don’t
really speak the
same language.