BIOTECHNOLOGY & YOU
a magazine of biotechnology applications in healthcare, agriculture, the environment, and industry
Volume 7, Issue No. 1
Tissue
Engineering
Volume 7, Issue No. 1
Your World/Our World describes the application of
biotechnology to problems facing our world. We
hope that you find it an interesting way to learn
about science and engineering.
Development by:
The Pennsylvania Biotechnology Association,
The PBA Education Committee, and
Snavely Associates, Ltd.
Writing & Editing by:
The Writing Company, Cathryn M. Delude and
Kenneth W. Mirvis, Ed.D.
Design by:
Snavely Associates, Ltd.
Illustrations by:
Patrick W. Britten
Science Advisor:
Peter C. Johnson, M.D.,
Pittsburgh Tissue Engineering Initiative
Special Thanks:
The PBA is grateful to the members of the
Education Committee for their contributions:
John C. Campbell, SmithKline Beecham
Kathy Cattell, SmithKline Beecham
Ceil M. Ciociola, PRIME, Inc.
Jeff Davidson, Pennsylvania Biotechnology
Association
Alan Gardner, SmithKline Beecham
Cynthia Gawron-Burke
Anthony Green, Puresyn, Inc.
Barbara Handelin, Handelin & Associates
Mary Ann Mihaly Hegedus, Bioprocessing Resource
Center
Linda C. Hendricks, SmithKline Beecham
Daniel M. Keller, Keller Broadcasting
Richard Kral
Colleen McAndrew, SmithKline Beecham
Barbara McHale, Gwynedd Mercy College
June Rae Merwin, The West Company
M. Kay Oluwole
Lois H. Peck, Philadelphia College of
Pharmacy & Science
Jean Scholz
John Tedesco, Brandywine Consultants, Inc.
Adam Yorke, SmithKline Beecham
Laurence A. Weinberger, Esquire,
Committee Chair
If you would like to make suggestions or comments
about Your World/Our World, please contact us at:
Internet: 73150.1623@compuserve.com
or write to:
Pennsylvania Biotechnology Association
1524 W. College Avenue, Suite 206
State College, PA 16801
Copyright 1997, PBA. All rights reserved.
2
Tissue Engineering
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BIOTECHNOLOGY & YOU
TABLE OF
CONTENTS
Tissue Engineering
3
4
6
8
10
12
14
15
16
Tissues Under Repair: From
Ancient Greece to Tomorrow
Tissue Construction Site
Differentiation: How Does a
Cell Know What Cell to Be?
New Products: Skin, Bones,
& More
Under Design:
Complex Organs
Parallel Technologies
PROFILE
Doris Taylor
ACTIVITY
“Reverse” Tissue Engineering
References
On the Cover: In the future of tissue engineering, a computer will help design human
body replacement parts using specially grown and engineered cells.
Tissues Under repair:
From Ancient Greece to Tomorrow
Ancient Greeks told a tale about how the
king of the gods, Zeus, punished Prometheus
for stealing fire and giving it to people. Zeus
tied Prometheus to a cliff and sent an eagle
to eat Prometheus’s liver during the day. But
every night, the “immortal” liver grew back
to its original
size.
I
n truth, if part of our
liver is destroyed, it
can heal andgrow back to
the same size. Likewise, our
skin heals after a cut and broken
bones mend. This ability of our
body to repair itself is called regeneration. Throughout the ages, people
have wondered why some parts of our
bodies regenerate and others, such as
nerves and intestines, don’t.
The answer lies in the nature of the
tissue. A tissue is a group of specialized cells that do a unique job. Your
body has a huge variety of tissues,
and each tissue looks completely
different from those with other
functions in the body. In addition,
most tissues work in a larger unit
called an organ, such as your brain,
liver, stomach, and skin. Each organ
has a unique shape and structure
specifically designed so it can
perform its function in your body.
For example, specialized cells called
neurons have long extensions that
pass along electrical signals. Together,
these cells form a tissue that processes the many complicated signals
to and from the body. This tissue
works alongside blood vessels,
membranes, and connective tissues
in the organ we call the brain.
body. Their success will bring lifesaving relief to people whose tissues
or organs are too badly damaged to
heal themselves.
This field, called tissue engineering,
is still very new. Some of its applications are already making breakthroughs in the way doctors can
treat damaged skin, cartilage, and
bones. The work on more complicated organ tissue, such as muscles,
heart, and liver, is just beginning. In
this issue of Your World/Our World,
you will read about this exciting
field. Put on your hard hats, because
we’re heading to a tissue construction site!■
Scientists are studying the way your
own body builds its many specialized tissues and uses them to
construct complex organs. They
are learning how the cells surrounding a tissue affect the way
that tissue develops, how it
functions when healthy, and
how it can heal when it is
injured. They are using this
understanding to make or
“engineer” tissues that can
function properly in the
Pennsylvania Biotechnology Association
Pennslyvania
3
TISSUE
SITE
Your Body, Your House
Support Scaffolding
ach room in your house has
several different “systems”,
such as plumbing, electricity,
and flooring. Each system has a
particular structure that helps it
perform its function. For instance,
the long, strong, round pipes of
the plumbing system are specifically designed for the job of
carrying water and sewage.
Carpenters use scaffolding
so they can place materials in
the right place on a building. A tissue
also has a scaffold that supports its
ongoing construction. The scaffold
determines the three-dimensional
shape that the tissue will take, such
as whether it will be part of a knobby
knuckle, a long shin bone, or a round
eyeball. Scientists call this scaffold
the extracellular matrix because it is
made of material outside the cells –
“extracellular” – and a matrix is a 3-D
structure with spaces to be filled.
E
An organ in your body is like a
room in a house, made up of
several tissues. For example, your
heart has muscles, blood vessels,
valves, membranes, nerves, and
connective tissues. All these tissues
have a unique structure that allows
the heart to function. The flexible
tubes of blood vessels let blood flow
through them, for example, while
the muscle fibers
stretch and contract
to pump the blood.
4
Tissue Engineering
A tissue’s scaffold is made of
material uniquely suited to encourage a particular quality in the
tissue’s cells. For
example, skin has a
jelly-like scaffold
material with
collagen, a protein
that gives the tissue an
elastic quality. Bone scaffold
also contains collagen, but
during development the
bone cells deposit calcium and
proteins in the scaffold, giving the
bone rigidity and strength.
Tissue engineers are now learning to
imitate a tissue’s natural scaffold.
They create a biomaterial,
which is a human-made
substance that mimics the
structure and function
of a living (“bio”)
material. A biomaterial
scaffold is like a honeycomb that provides the
outline shape the tissue will
grow to fill. But first, tissue
engineers grow cells of
that tissue type in a
culture, which is a
nutrient-rich fluid that
allows cells to divide
many times to create a large
number of identical cells.
When cells grow in a
culture dish or flask, they
act like individual cells.
But when they grow in a
three-dimensional scaffold, they
These images show cross
sections of the chest, head, and
thorax taken from the National
Library of Medicine’s “Visible
Human” Project (http:/
www.nlm.nih.gov/research/
visible/visible_human.html).
How many different tissues
can you identify in these
views? What are their
functions in the organs?
How many other organs
and their functions can you
identify?
act like members of a larger community – a tissue. When scientists place
these cells in the honeycomb scaffold,
the cells reproduce and fill the spaces
in the scaffold. In this way, they form
a tissue with the right three-dimensional shape. Tissue engineers can
grow the tissue inside a sealed, sterile
incubator called a bioreactor and
then place it in the body. They can
also place the scaffold in the body so
the tissue grows in place. Gradually,
the biomaterial scaffold degrades as
living tissue replaces it.
Tissue engineers can even fine-tune
this tissue growth. They place
proteins in the scaffold that make
cells attach to specific sites. The
cells then divide at these sites to
form the desired tissue structure.
They can also add molecules known
as growth factors – specialized
molecules produced by our own
bodies that make our cells divide at
a specific rate. These growth factors
make cells grow at a certain speed
or in a certain direction. These
techniques are already being used
to build new skin and bones. (See
pages 8-9.)
To build more complex tissues,
scientists are developing an even
more advanced technology that
does not use a pre-made scaffolding.
It will work like a three-dimensional
printer, using computers to lay
down one layer of biomaterial at a
time. Each layer will have a specific
pattern and will build upon the
previous layer to create a complex
3-D structure. Tiny robots with
grippers and laser tweezers move
single cells in the biomaterial.
Together, the computer and microrobots will build a tissue in a
completely controlled fashion. ■
Cells are placed in a biomaterial scaffold, within
which they can multiply and form a developing tissue.
Pennsylvania Biotechnology Association
Pennslyvania
5
Differentiation:
How Does a Cell Know
What Cell to Be?
A Colony of Tissues
In a way, tissues are like members of an ant colony.
Different members have separate functions to keep the
colony alive and healthy. Ants start out the same, but
they become specialized as they develop. Some become
workers, guards, or caretakers of the young, and one
becomes the queen. Yet they all work together for the
good of the colony.
Likewise, our many tissues develop from the same
fertilized human egg. The cells that become brain tissue,
lips, and liver all start out the same. Through a series of
divisions, they become different types of cells with
unique structures and functions. This process is called
differentiation.
The cells in liver and skin look different
because they have different functions.
Yet they both developed from the same
undifferentiated cells in the embryo.
6
Tissue Engineering
For tissue engineering to succeed,
we need to know more about how
cells differentiate and develop into
individual tissues. Like plants in a
garden coming up at certain times
throughout spring, summer, and
fall, each tissue has an expected
time and place of development.
Guiding this development requires
a set of environmental cues. For
plants, those cues may be the
amount of light, temperature, and
moisture. For tissues, these environmental cues may be hormones
or other signals near the cells.
Stem Cells
grow in the right places in the
biomaterial. Thus, tissue-specific
stem cells are very valuable in tissue
engineering because they can repair
the same type of tissue.
The stem cells in bone marrow are
even more remarkable. The bone
marrow is the soft material inside
our bones that makes new blood
cells and produces the numerous
types of immune cells that help us
fight disease. Some of the bone
marrow’s stem cells produce all the
types of blood cells to meet the
body’s needs. Other bone marrow
cells can produce cells for fat,
cartilage, muscles, tendons, and
other tissues! In the future, tissue
engineers may be able to coax a
bone marrow stem cell into producing the differentiated cells and tissue
structure to repair damage elsewhere in the body.■
A Database on Development
Developmental biology studies the
timing and sequence of tissue
development. Changes in tissues
occur over the course of an
individual’s life. Computers are
helping us track changes in a
tissue’s shape and function over
time. This information will help
scientists create more life-like
tissues.▼
In most towns, there are probably a
few people who could reproduce the
structure and function of the town’s
government if the town hall burned
down. In the same way, many
tissues have a few cells with enough
knowledge to reproduce the whole
tissue. These “smart” cells are
tissue-specific stem cells. Unlike
other specialized cells, stem cells are
immature; that is, they are not very
differentiated. Their job is to
provide new cells for the
ells
tissue. When the tissue
em c
t
s
rrow
for
needs a specialized cell, a
e ma aluable une
n
o
B
v
m
y
stem cell reproduces,
r
e ve ng the im g or
r
a
i
dividing into two “daughter”
ild
dru
as
rebu
after tment h one
cells. One daughter is a
m
e
a
syst ion tre tient’s b
specialized cell, while the
t
a
radia yed a p
other is another stem cell.
o
r
t
s
de
row.
In a sense, tissue-specific stem
mar
cells have the blueprint for that
tissue. They make sure that cells
Pennsylvania Biotechnology Association
7
N E W
P R O D U C T S :
Skin,Bones,
& more
area. However, this skin graft method damages the body
where the skin is removed, and sometimes there is not
enough healthy skin to use. The body routinely rejects
grafts from other people.
Developing a way to save burn victims and others has
been one of the first goals of tissue engineering – and
an early success. One method uses cells called fibroblasts from the deep layer of skin called the dermis.
Unlike the muscle cells you will read about in the next
article, fibroblast cells divide readily to reproduce.
Scientists create sheets of biomaterial scaffolding
containing collagen, a protein naturally found in skin.
Inside this scaffold, the fibroblasts grow into a layer of
dermis. Doctors place this layer on the patient’s
wounded surface, where it begins to establish a blood
supply and live on its own. To create the epidermis,
scientists grow keratinocytes cells that make up this
thinner, outer layer of skin. When these cells form a
thin sheet, they can be placed on top of the dermis
layer.
Bones: Pillars of the Body
New layers of skin will seal and protect this
wounded area.
Skin: Your Body’s Shield
Your skin protects you from invading organisms, controls
your body temperature, contains touch and pressure
sensors that alert you to danger, and keeps your organs
on the inside! In the course of your life, your skin has
probably healed from some pretty painful cuts, scrapes,
and burns. But sometimes skin can become so badly
injured that it cannot grow back. In that case, a person
can die from infections. The only hope is to replace the
lost skin with new skin.
Traditionally, doctors remove healthy skin from one part
of the patient’s body to “graft” or place on the damaged
8
Tissue Engineering
Broken bones usually heal, but sometimes not perfectly.
Cancers and other diseases of the bones can
destroy them, and many people are
born with missing or
deformed bones.
necCon
e
c
Bones have several
ien
& Sc means
k
components: minerals to
e
Gre Osteo t comes ak.”
:
s
give them hardness;
tion e.” Cla “to bre stos,
n
proteins to give them
o
e
t s,
Bla
“b
Klos s from
strength; blood vessels to
m
e
fro
t com
nourish them; and special
Blas ud.”
b
cells that build and remodel
“to
them. These special cells are
osteoblasts and osteoclasts.
Osteoblasts build bone material
to make it thicker and stronger
at certain sites. Osteoclasts
dissolve bone. Together, they
form a team that grows and
remodels bones throughout life as
you grow taller, stronger, heavier, and older.
When cartilage in a joint is damaged, the bones grind
together, causing pain and damaging bones. Repairing
joints can restore athletes to the playing fields and keep
people off crutches and out of wheelchairs.
Such repairs have become fairly common these past
decades. They help keep people active, but they are not
perfect. A standard replacement part is made of metal or
plastic molded to the shape of a normal hip joint. This solid
material permanently replaces the entire joint. It cannot
grow and remodel itself as the person grows and ages. After
ten or twenty years, it often needs to be replaced again.
Tissue engineers are working to overcome these problems. They are developing a hip replacement using new
biomaterials that can become part of the living, growing, changing body. It
begins as a porous
scaffold with space for
the cartilage cells to
grow. These cells
gradually replace the
biomaterial, leaving a
“living” joint that can
grow and change along
with the body.
This collagen scaffold molds the shape for a
new, cushioning joint.
Tissue engineers can use the osteoblasts to grow new
bones. They place these bone-grower cells in a biomaterial scaffolding with the mineral component of bone. The
cells use this structure for support while they produce the
proteins and minerals to grow new bones. Placing growth
factors in key areas of the scaffold helps shape the bone
growth. In some cases, the scaffold is placed right on the
bone defect in the patient, and new bone tissue grows
into the scaffolding.
Tissue engineers hope to be able to design a bone to
match the shape of an individual patient. Computers will
help by layering cells and biomaterials in two dimensions
at a time, building towards the complex three dimensional structure of a real bone.
Another method is
already being
introduced.
Doctors inject
cartilage into a
patient’s
injured joint.
There, the
cells rejoin
the damaged
cartilage and
become
anchored to the
surrounding
tissue.
In the future, doctors
will be able to use
cartilage to rebuild a
badly injured nose,
Cartilage: Shock Absorbers
cheek bone, or jaw.
Many an athlete has been brought
They hope to be able
Sin
down by damaged cartilage.
to inject cartilage
c
r
e
e
Cartilage is the cushioning tissue
The bone cells in this biomaterial scaffold will
tissue with a soft
ca quir cart
in our joints and knuckles, and
produce proteins and deposit minerals to
en n su e a ilag
biomaterial scaffold
make the bone as good as new.
it gives shape to our noses
th ts fr rviv blo e do
that
gels
at
o
a
o
and ears. It has a texture
an t h m e o d s es
body temperature to take a desired shape. After
Es d fr ave nea n th upp not
like a cake of dry soap.
ta
om bl rb e
several months, the cartilage cells will replace
l
y
s
b
u
o
When lubricated by
y nu , it
l
that scaffold, forming a cartilage tissue with the
tis tri
hu pply ishi join od
s
joint fluids, it prom rdle re ng a t flu supp ues
same contour. Thus, the face will be rebuilt from the
or
m
vides a slippery
i
l
e c for ain blo d. ies
inside, without the pain, expense, and difficulties of
od
om en s
surface for the bones
plastic surgery.■
pl gin a m
in our joints.
ex e
aj
e
o
tis rin r
su g
es
.
Pennsylvania Biotechnology Association 9
Complex Organs
Heart: Power Supply of the Bloodstream
The heart is an incredibly complex organ. In addition
to its four chambers, it has a muscular wall, blood
vessels, an electrical system, and large valves to direct
the flow of blood between chambers. Fortunately, when
a heart goes bad, we can replace heart valves and blood
vessels, and sometimes the heart itself. However, the
supply of healthy hearts for heart transplants is very
limited, and a patient’s immune system often rejects the
“foreign” organ.
Tissue Engineering may eventually overcome problems
of shortage and rejection. Tissue engineers can already
grow heart valves using biomaterials and human cells.
They are working on ways to grow blood vessels and to
Constructing a heart requires plumbing (to pump blood
through its pipelines), electricity (to wire the electrical
impulses), doors (valves directing blood to different
chambers), frames (muscles, walls, connective tissues),
and sheet rock (membranes).
10
Tissue Engineering
strengthen the heart walls by transferring muscle cells
from the limbs to the heart. (See the Profile on page
14.) One day they may be able to engineer an entire
three-dimensional heart shaped muscle to replace the
heart itself.
Liver: Setting the Body Right
Perhaps less famous than the heart, the liver is equally
complex and vital. It creates proteins, protects against
infection, removes toxins from the blood, and helps
digest food. To do all these tasks, it has two blood
supplies, ductwork for the removal of bile, and a unique
tissue structure that allows it to process
body fluids.
When a liver becomes badly damaged
by disease or alcohol abuse, the
patient will die unless a rare liver
transplant is available. To help
people waiting for a transplant,
tissue engineers created a
partial replacement liver. This
structure contains liver tissue
in a biomaterial casing.
It is attached to a patient’s
arteries and veins but
remains outside the
Creating this artificial liver was made
possible by a breakthrough in cell
growth technology. Until recently, no
one could grow human liver cells in a
laboratory culture. Scientists used
computers to test all the possible
combinations of nutrient fluids that
liver cells might need to grow. The
computer helped them identify the
right mixture for growing liver cells.
Tissue engineers can now grow the
cells that will eventually be used to
engineer a working liver tissue.
Many diseases such as muscular
dystrophy cause muscles to degenerate. In some cases, people lose
strength in the large muscles, such
as those that move arms, legs, and
the head. In advanced cases, people
also lose the involuntary muscles
that allow them to eat, breathe, and
digest food. They need respirators
and feeding tubes to survive. Thus,
learning to repair and strengthen
muscles could prevent a lot of
human misery. Tissue engineers are
hoping to do just that.
Tahsin Oguz Acarturk, MD, Paul A. DiMilla, Ph.D, and Patti Petrosko, MS
When muscle cells grow in a laboratory culture, they join together to
become fibers. If the culture is
“stretched” the way real muscles
stretch, these fibers form very thin
In the future, we may have the technology to make replacement tissues and organs
for any individual. Clearly, these replacement parts could solve many life-threatening medical problems. But, like most scientific advances, these benefits may be
complicated by difficult choices. Here are some of the concerns scientists have:
1) Availability: Who will get a replacement part if there are not enough resources
to make one for everybody who needs one? Will young people be favored over
old? People who have taken care of their bodies over people who abused them
with cigarettes and alcohol? Who will set the priorities?
2) Cost: Engineered tissues will be expensive. Will only wealthy people be able to
afford them? Should health insurance companies cover them for everybody? Will
we begin to think we have a “right” to new tissues?
3) Age: How late in life should we keep replacing organs? Should there be a cutoff age? Should we keep trying to rebuild worn-out bodies?
muscle-like tissues. Tissue engineers
can coax the muscles to form a
predictable structure. To do so, they
use laser patterning techniques
similar to those used to make printed
circuit boards for electronics. They
“print” a pattern on the biomaterial
where cells will attach. The patterns
imitate the structure of a particular
type of muscle.
ABOU
If you could go
in for a “tissue
tune up” every
twenty years,
would you still
try to take care
of your body, or
would you just wait
for a tissue “upgrade?”
!
T THIS
Muscles: Moving Through Life
SpareParts:WhoGetsThem?
N
THI K
body. When the blood flows through
the device, the liver cells perform
their functions
in cleaning the blood and digesting
food. This device can keep a patient
alive until a transplantable liver can
be found.
The next challenge for tissue engineers is to find a
way to make
blood vessels and
nerve cells grow
into muscles.
Then, these
muscles may be
used to treat
paralysis or
muscular
weakness.■
These are magnified images of myoblasts patterned on biomaterials.
The image on left shows very narrow adhesive lines and the image on right shows
wider adhesive patterns.
“Hearts!?? No, No, …We wanted livers!”
Pennsylvania Biotechnology Association
11
Parallel
Technologies
T
o build a house, we have to know how it will look
on the outside, what its internal structure will be,
and the stages in which different parts will be
built. Tissue engineers need to know similar things to
build a new tissue: how a real tissue looks inside
and out, how it works with other tissues, and how it
develops and grows.
A Study in Tissues
When people first studied tissues, they were fascinated
by the differences in texture, color, form, and function.
People from the past would be amazed at how completely
we can now “see” tissues. The National Library of
Medicine’s “Visible Human” project shows a slice by slice
view of a body from the inside. (See graphic on page 4.)
Each view is digitized on the computer, so scientists can
pluck a “virtual” tissue from the body, turn it, and study
its shape, texture, and organization. This ability will help
tissue engineers manufacture artificial tissues.
The invention of the microscope allowed people to see
that many individual cells are the building blocks of
tissues and to observe how the structure of tissues affects
their function. Today, new imaging methods provide
glimpses of how tissues look in action in living animals
and humans. These images provide the foundation for
learning how to build replacement tissues that will
function properly in the body.
The relatively new study of genes allows us to understand
the cells within tissues on a genetic level. The international Human Genome Project has identified many genes
responsible for the structure and function of tissues.
Tissue engineers may be able to use this knowledge to
change a diseased tissue by inserting a healthy gene in it,
or to create customized replacement tissues.■
12
12
Tissue Engineering
Tissue Engineering
Technologies Working Together
Growing complex tissues involves four important areas of science and technology: cell
biology, molecular biology, biomaterials science,
and computer-assisted design and manufacture.
Cell biology shows us how cells grow and develop to
form different tissues. It provides techniques for
growing cultures of specific cells at specific rates, and
knowledge about growth factors and other molecules
that affect cell growth and activity.
Molecular biology teaches us how genes control cell
development and how to control differentiation.
Biomaterials science give us the ability to make
substitute tissues that can work in harmony with the
body.
Computer-assisted design and manufacturing
allows us to control precisely the sequence and
pattern of cell growth to create a 3-D tissue.
Many other technologies also contribute
to tissue engineering:
• Microscopic imaging techniques show the structure of
tissues at the cellular level;
• Micro-robotics and cell grippers place cells and scaffolding together;
• Polymer chemistry develops appropriate materials and
structures for biomaterial scaffolding;
• Computers handle the information needed for tissue
engineering;
• Manufacturing helps build biomaterials and incubators
(bioreactors) for growing and nurturing tissues.
Thus, many diverse areas contribute to tissue engineering
and offer exciting and valuable career opportunities for
today’s students and tomorrow’s scientists.
NASA Tissue Research
If tissue engineering sounds “space
age,” consider this. Scientists at
NASA are growing tissues both
aboard the Space Shuttle and at the
Johnson Space Center in Houston.
Why? Because earthbound scientists
have found that, in some situations,
gravity interferes with the way
engineered tissues grow in the
laboratory. They do not develop the
proper shape of natural tissues.
Tissues grown on the Space Shuttle or
in the Space Center’s “microgravity
bioreactor”— which is an incubator
for growing cells without the influence
of gravity — have a more natural
structure. Eventually, these experiments may help us learn how to
develop more natural-looking tissues
in our natural gravitational environment. After all, our own tissues grow
normally in gravity!▼
Pennsylvania Biotech Association
Pennsylvania Biotechnology Association
13
13
Profile:
Doris Taylor, Assistant
Research Professor
Doris Taylor runs a laboratory in the Departments of
Medicine and Surgery at Duke University Medical
Center. She has a B.S. in biology and physical
science from Mississippi University for Women and a
Ph.D. in Pharmacology from Southwestern Medical
School in Dallas. She did post-doctoral work in
cardiac (heart) molecular biology at Albert Einstein
College of Medicine in New York.
D
oris Taylor’s research may
provide a long-awaited cure
for a common type of heart
disease called congestive heart
failure. This heart failure often
follows a heart attack, which scientists call acute myocardial infarction. Myocardial refers to the muscle
(“myo”) of the heart (“cardia”), and
infarction means damage from lack
of blood (usually because the artery
is clogged). After a heart attack, the
damaged portion of the heart
muscle dies, and the heart eventually fails. “The heart cannot repair
the damaged muscle because its
muscle cells cannot reproduce,”
Doris explains. “You are born with
all the heart cells you will ever
have. Your heart grows because the
cells become larger, not because
they multiply.”
However, other muscles do have the
ability to repair themselves because
they contain cells called myoblasts,
which can reproduce. Myoblasts are
immature tissue-specific stem cells
in muscles that can produce more
specialized muscle cells when
needed. “We are always damaging
our skeletal muscles – the ones that
move our bones – when we strain
them or bump into things,” Doris
continues. “When our skeletal
muscles are damaged, they stimulate the myoblasts to reproduce and
make more muscle cells to repair
the damage.”
Doris asked herself, “Why don’t we
take skeletal myoblasts and see if we
can transplant them into the heart
and get them to live there?” She
hoped that the transplanted myo-
1414Tissue
Engineering
Tissue
Engineering
blasts might reproduce as they do in
skeletal muscles and replace the
damaged heart cells. Her laboratory
experiments with animals show that
the myoblasts do seem to help the
heart muscle repair itself!
Every year in the United States, about
half a million people have heart attacks.
Many of them go on to develop heart
failure – a leading cause of death in
people over 65. Doris envisions the
following scenario. “When someone
comes into the emergency room with a
heart attack, we take a tiny bit of
muscle from their arm or leg and
extract the myoblast cells. The ER
doctors continue with their usual
treatment, and we take the myoblasts
to the lab to grow them in a culture.
After a few weeks, when we have
10,000,000 or more myoblasts, we
implant them into the patient’s damaged heart muscle, and that patient will
soon have a repaired heart instead of
one that is likely to fail again.”
The next area of research is to find
ways to make the myoblasts more
heart-like. “If we put them in the
kind of extracellular matrix found in
the heart, and then stretch them to
simulate a beating heart, perhaps they
will become more heart-like. For
example, maybe they will form the
kind of electrical connections that
other heart cells have. That would be
incredibly important!”■
I
ACTIVITY:
!
“Reverse” Tissue Engineering
VI
In this activity, you will see first
hand what happens when bones
become demineralized. To understand what happens, you should
know that acids can leach (dissolve) minerals out of other substances. Acid rain can leach mineral
nutrients out of soil, and acidic
water can leach dangerous metals
such as lead and copper out of pipes.
In the same way, acids can leach
calcium out of bones.
Materials
• Three cooked chicken thigh
bones
• Two 250 mL beakers
• Vinegar
• Distilled water
Procedure
1) Examine the thigh bones and
note the different kinds of tissues
you see. Draw a diagram of the
bone and label the tissues.
2) Place a bone in a beaker and pour
in vinegar to cover.
3) Place a second bone in a beaker
and pour in distilled water.
250 ml
125 ml
250 ml
125 ml
If you were a tissue
engineer, how
would this activity
help you understand what kind of
scaffold you would
need to design to
engineer a bone?
What kind of cells would you
“plant” in the scaffold?
ABOU
T THIS
You have probably learned that
calcium builds strong bones. Your
bones actually start out fairly soft and
flexible. The bone tissue develops
around a scaffold made of elastic
fibers and collagen, which is the soft,
flexible material that also forms the
scaffold of cartilage and skin. As
bones develop, the bone cells deposit
the mineral calcium in the scaffold.
This calcium gives bones more
strength, density, and mass.
Bones are dynamic tissues that are
always losing and gaining calcium.
As you grow old, your bones tend to
lose more than they gain. To
keep your bones strong, you
need to add calcium to your
bones throughout your life.
Otherwise, your bones will lose
their density and mass
because they are losing
calcium. This loss of
calcium causes
broken bones, bent
backs, and
shrinking height.
Have you ever
seen a stooped
over old person or
someone with a
“dowager’s
hump?” Their
vertebrae are so
demineralized
that they collapse.
N
THI K
Strong Bones/Weak Bones
4) Allow the bones to soak for
three days.
5) After three days, remove the
bones and rinse under running
water.
6) After the bones have dried, place
them next to the third, untreated
chicken bone. Compare the way
the three bones look and record
your observations.
7) Now test and compare the
flexibility and rigidity of the three
bones by trying to bend and twist
them. Record your comparisons.
Conclusions
1) Did either of the two liquids affect
the flexibility and strength of the
bone?
2) Which of the two liquids do you
think is acidic?
3) Which of the soaked bones shows
what the bone’s scaffold is like
before it becomes mineralized?
Extensions
1) Describe how the bone structures of a new born baby, a
teenager, and an elderly person
differ.
2) The loss of bone mass in older
adults is called osteoporosis, and
it is a major health issue for the
elderly. Find out more
about why people lose
their bone mass, what
you can do to
prevent it happening
to you, and why you
should start now! ■
Pennsylvania Biotechnology Association
15
References
Websites:
Pittsburgh Tissue Engineering
Initiative, Inc. (PTEI):
http://www.pittsburgh-tissue.net/
Visible Human Project: http://
www.nlm.nih.gov/research/
visible/visible_human.html
Human Genome Project: http://
www.nhgri.nih.gov/
For a “fly through” video
simulation visit General Electric’s
Research & Development site:
Three Dimensional Medical
Reconstruction at: http://
www.crd.ge.com/esl/cgsp/
projects/medical/
Dear Students:
B
iotechnology and the rapid advances of science are in the
news often because they are providing new opportunities for
improving human and animal health, agriculture, and the
restoration of damaged environments. This issue of Your World/
Our World is designed to allow you to explore how biotechnology
will influence your life and your world by introducing you to the
new area of tissue engineering. Research in this area is underway to
discover how tissues can be restored, maintained, or replaced by
engineering or creating new tissues.
We hope that greater understanding of emerging scientific areas will
encourage you to continue to study science and mathematics. We
also welcome your selection of biotechnology as a career and your
participation as a co-discover of tomorrow’s science and technology.
Sincerely,
Other Issues of Your
World/Our World
Exploring the Human Genome
(Vol. 5, #2):
Jeff Davidson
Executive Director, Pennsylvania Biotechnology Association
The Human Genome Project
Investigating the Brain (Vol. 6, #1):
The structure and function of
the brain.
Organ
Function
Brain
Controls sensation,
muscles, thought
Heart
Pumps blood
throughout the body
Liver
Makes proteins,
assists digestion of
fat, removes toxins
Intestine
Digests food
Muscle
Moves the body
Bones
Supports body
structure, makes
blood cells (marrow)
Skin
Protects body,
provides touch
sensation, controls
temperature
Cartilage
16
Forms joints, ears,
and nose
Tissue Engineering
PBA would like to acknowledge Pittsburgh Tissue Engineering Initiative, Inc. for
their assistance and support in preparing this issue of Your World/Our World.
We are able to publish Your World/Our World only because of the support of the
companies and organizations listed below. Please join us in thanking them for
their support:
Sponsors
The Alliance for Science Education
Biotechnology Industry Organization
Centocor, Inc.
Fisher Scientific, Inc.
Merck Institute for Science Education
Pasteur Mérieux Connaught
Rhône-Poulenc Rorer Gencell
TosoHaas
Supporting Organizations
Utah State University Biotechnology Center
Massachusetts Biotechnology Council
Maryland Bioscience Alliance