biotechnology & you - biotech institute

Volume 7, Issue No. 1

BIOTECHNOLOGY & YOU

a magazine of biotechnology applications in healthcare, agriculture, the environment, and industry

TissueEngineering

2 Tissue Engineering

BIOTECHNOLOGY & YOU

C O N T E N T STABLE OF

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

3

Volume 7, Issue No. 1

Your World/Our World describes the application ofbiotechnology to problems facing our world. Wehope that you find it an interesting way to learnabout science and engineering.

Development by:The Pennsylvania Biotechnology Association,The PBA Education Committee, andSnavely Associates, Ltd.

Writing & Editing by:The Writing Company, Cathryn M. Delude andKenneth 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 theEducation Committee for their contributions:

John C. Campbell, SmithKline Beecham

Kathy Cattell, SmithKline Beecham

Ceil M. Ciociola, PRIME, Inc.

Jeff Davidson, Pennsylvania BiotechnologyAssociation

Alan Gardner, SmithKline Beecham

Cynthia Gawron-Burke

Anthony Green, Puresyn, Inc.

Barbara Handelin, Handelin & Associates

Mary Ann Mihaly Hegedus, Bioprocessing ResourceCenter

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 ofPharmacy & 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 commentsabout Your World/Our World, please contact us at:Internet: [email protected] write to:Pennsylvania Biotechnology Association1524 W. College Avenue, Suite 206State College, PA 16801

Copyright 1997, PBA. All rights reserved.

Tissues Under Repair: FromAncient Greece to Tomorrow

46

Tissue Construction Site

Differentiation: How Does aCell Know What Cell to Be?

8 New Products: Skin, Bones,& More

10 Under Design:Complex Organs

Parallel Technologies

14 Doris Taylor

15 “Reverse” Tissue Engineering

On the Cover: In the future of tissue engineering, a computer will help design humanbody replacement parts using specially grown and engineered cells.

A C T I V I T Y

12P R O F I L E

Tissue Engineering

16 References

Pennsylvania Biotechnology Association 3

Ancient Greeks told a tale about how theking of the gods, Zeus, punished Prometheusfor stealing fire and giving it to people. Zeustied Prometheus to a cliff and sent an eagleto eat Prometheus’s liver during the day. Butevery night, the “immortal” liver grew backto its original size.

Tissues

In truth, if part of ourliver is destroyed, itcan heal andgrow back to

the same size. Likewise, ourskin heals after a cut and brokenbones mend. This ability of ourbody to repair itself is called regen-eration. Throughout the ages, peoplehave wondered why some parts of ourbodies regenerate and others, such asnerves and intestines, don’t.

The answer lies in the nature of thetissue. A tissue is a group of special-ized cells that do a unique job. Yourbody has a huge variety of tissues,and each tissue looks completelydifferent from those with otherfunctions in the body. In addition,most tissues work in a larger unitcalled an organ, such as your brain,liver, stomach, and skin. Each organhas a unique shape and structurespecifically designed so it canperform its function in your body.For example, specialized cells calledneurons have long extensions thatpass along electrical signals. Together,these cells form a tissue that pro-cesses the many complicated signalsto and from the body. This tissueworks alongside blood vessels,membranes, and connective tissuesin the organ we call the brain.

Scientists are studying the way yourown body builds its many special-ized tissues and uses them toconstruct complex organs. Theyare learning how the cells sur-rounding a tissue affect the waythat tissue develops, how itfunctions when healthy, andhow it can heal when it isinjured. They are using thisunderstanding to make or“engineer” tissues that canfunction properly in the

Tissues Under repair:From Ancient Greece to Tomorrow

body. Their success will bring life-saving relief to people whose tissuesor organs are too badly damaged toheal themselves.

This field, called tissue engineering,is still very new. Some of its applica-tions are already making break-throughs in the way doctors cantreat damaged skin, cartilage, andbones. The work on more compli-cated organ tissue, such as muscles,heart, and liver, is just beginning. Inthis issue of Your World/Our World,you will read about this excitingfield. Put on your hard hats, becausewe’re heading to a tissue construc-tion site!■

Pennslyvania Biotechnology Association 3


T I S S U E

S I T E

Your Body, Your House

Each room in your house hasseveral different “systems”,such as plumbing, electricity,

and flooring. Each system has aparticular structure that helps itperform its function. For instance,the long, strong, round pipes ofthe plumbing system are specifi-cally designed for the job ofcarrying water and sewage.

An organ in your body is like aroom in a house, made up ofseveral tissues. For example, yourheart has muscles, blood vessels,valves, membranes, nerves, andconnective tissues. All these tissueshave a unique structure that allowsthe heart to function. The flexibletubes of blood vessels let blood flowthrough them, for example, while

the muscle fibersstretch and contractto pump the blood.

bone cells deposit calcium andproteins in the scaffold, giving thebone rigidity and strength.

Tissue engineers are now learning toimitate a tissue’s natural scaffold.

They create a biomaterial,which is a human-madesubstance that mimics thestructure and function

of a living (“bio”)material. A biomaterialscaffold is like a honey-comb that provides theoutline shape the tissue willgrow to fill. But first, tissueengineers grow cells ofthat tissue type in aculture, which is anutrient-rich fluid thatallows cells to dividemany times to create a largenumber of identical cells.

When cells grow in aculture dish or flask, they

act like individual cells.But when they grow in a

three-dimensional scaffold, they

Support ScaffoldingCarpenters use scaffoldingso they can place materials inthe right place on a building. A tissuealso has a scaffold that supports itsongoing construction. The scaffolddetermines the three-dimensionalshape that the tissue will take, suchas whether it will be part of a knobbyknuckle, a long shin bone, or a roundeyeball. Scientists call this scaffoldthe extracellular matrix because it ismade of material outside the cells –“extracellular” – and a matrix is a 3-Dstructure with spaces to be filled.

A tissue’s scaffold is made ofmaterial uniquely suited to encour-age a particular quality in thetissue’s cells. Forexample, skin has ajelly-like scaffoldmaterial withcollagen, a proteinthat gives the tissue an

elastic quality. Bone scaffoldalso contains collagen, butduring development the


act like members of a larger commu-nity – a tissue. When scientists placethese cells in the honeycomb scaffold,the cells reproduce and fill the spacesin the scaffold. In this way, they forma tissue with the right three-dimen-sional shape. Tissue engineers cangrow the tissue inside a sealed, sterileincubator called a bioreactor andthen place it in the body. They canalso place the scaffold in the body sothe tissue grows in place. Gradually,the biomaterial scaffold degrades asliving tissue replaces it.

Tissue engineers can even fine-tunethis tissue growth. They placeproteins in the scaffold that makecells attach to specific sites. Thecells then divide at these sites toform the desired tissue structure.They can also add molecules knownas growth factors – specialized

These images show crosssections of the chest, head, andthorax taken from the NationalLibrary of Medicine’s “VisibleHuman” Project (http:/www.nlm.nih.gov/research/visible/visible_human.html).

How many different tissuescan you identify in theseviews? What are theirfunctions in the organs?How many other organsand their functions can youidentify?

molecules produced by our ownbodies that make our cells divide ata specific rate. These growth factorsmake cells grow at a certain speedor in a certain direction. Thesetechniques are already being usedto build new skin and bones. (Seepages 8-9.)

To build more complex tissues,scientists are developing an evenmore advanced technology thatdoes not use a pre-made scaffolding.It will work like a three-dimensionalprinter, using computers to laydown one layer of biomaterial at atime. Each layer will have a specificpattern and will build upon theprevious layer to create a complex3-D structure. Tiny robots withgrippers and laser tweezers movesingle cells in the biomaterial.Together, the computer and micro-robots will build a tissue in acompletely controlled fashion. ■

Cells are placed in a biomaterial scaffold, withinwhich they can multiply and form a developing tissue.

Pennslyvania Biotechnology Association 5


Differentiation:A Colony of TissuesIn a way, tissues are like members of an ant colony.Different members have separate functions to keep thecolony alive and healthy. Ants start out the same, butthey become specialized as they develop. Some becomeworkers, guards, or caretakers of the young, and onebecomes the queen. Yet they all work together for thegood of the colony.

Likewise, our many tissues develop from the samefertilized human egg. The cells that become brain tissue,lips, and liver all start out the same. Through a series ofdivisions, they become different types of cells withunique structures and functions. This process is calleddifferentiation.

The cells in liver and skin look differentbecause they have different functions.Yet they both developed from the sameundifferentiated cells in the embryo.

How Does a Cell KnowWhat Cell to Be?How Does a Cell KnowWhat Cell to Be?


Differentiation:


Bone marrow stem cells

are very valuable for

rebuilding the immune

system after drug or

radiation treatment has

destroyed a patient’s bone

marrow.

For tissue engineering to succeed,we need to know more about howcells differentiate and develop intoindividual tissues. Like plants in agarden coming up at certain timesthroughout spring, summer, andfall, each tissue has an expectedtime and place of development.Guiding this development requiresa set of environmental cues. Forplants, those cues may be theamount of light, temperature, andmoisture. For tissues, these envi-ronmental cues may be hormonesor other signals near the cells.

Stem CellsIn most towns, there are probably afew people who could reproduce thestructure and function of the town’sgovernment if the town hall burneddown. In the same way, manytissues have a few cells with enoughknowledge to reproduce the wholetissue. These “smart” cells aretissue-specific stem cells. Unlikeother specialized cells, stem cells areimmature; that is, they are not verydifferentiated. Their job is toprovide new cells for thetissue. When the tissueneeds a specialized cell, astem cell reproduces,dividing into two “daughter”cells. One daughter is aspecialized cell, while theother is another stem cell.

In a sense, tissue-specific stemcells have the blueprint for thattissue. They make sure that cells

A Database on DevelopmentDevelopmental biology studies thetiming and sequence of tissuedevelopment. Changes in tissuesoccur over the course of anindividual’s life. Computers arehelping us track changes in atissue’s shape and function overtime. This information will helpscientists create more life-liketissues.▼

grow in the right places in thebiomaterial. Thus, tissue-specificstem cells are very valuable in tissueengineering because they can repairthe same type of tissue.

The stem cells in bone marrow areeven more remarkable. The bonemarrow is the soft material insideour bones that makes new bloodcells and produces the numeroustypes of immune cells that help usfight disease. Some of the bonemarrow’s stem cells produce all thetypes of blood cells to meet thebody’s needs. Other bone marrowcells can produce cells for fat,cartilage, muscles, tendons, andother tissues! In the future, tissueengineers may be able to coax abone marrow stem cell into produc-ing the differentiated cells and tissuestructure to repair damage else-where in the body.■


N E W P R O D U C T S :

Skin: Your Body’s ShieldYour skin protects you from invading organisms, controlsyour body temperature, contains touch and pressuresensors that alert you to danger, and keeps your organson the inside! In the course of your life, your skin hasprobably healed from some pretty painful cuts, scrapes,and burns. But sometimes skin can become so badlyinjured that it cannot grow back. In that case, a personcan die from infections. The only hope is to replace thelost skin with new skin.

Traditionally, doctors remove healthy skin from one partof the patient’s body to “graft” or place on the damaged

Greek & Science Connec-

tion: Osteo means

“bone.” Clast comes

from Klostes, “to break.”

Blast comes from Blastos,

“to bud.”

area. However, this skin graft method damages the bodywhere the skin is removed, and sometimes there is notenough healthy skin to use. The body routinely rejectsgrafts from other people.

Developing a way to save burn victims and others hasbeen one of the first goals of tissue engineering – andan early success. One method uses cells called fibro-blasts from the deep layer of skin called the dermis.Unlike the muscle cells you will read about in the nextarticle, fibroblast cells divide readily to reproduce.Scientists create sheets of biomaterial scaffoldingcontaining collagen, a protein naturally found in skin.Inside this scaffold, the fibroblasts grow into a layer ofdermis. Doctors place this layer on the patient’swounded surface, where it begins to establish a bloodsupply and live on its own. To create the epidermis,scientists grow keratinocytes cells that make up thisthinner, outer layer of skin. When these cells form athin sheet, they can be placed on top of the dermislayer.

Bones: Pillars of the BodyBroken bones usually heal, but sometimes not perfectly.Cancers and other diseases of the bones candestroy them, and many people areborn with missing ordeformed bones.

Bones have severalcomponents: minerals togive them hardness;proteins to give themstrength; blood vessels tonourish them; and specialcells that build and remodelthem. These special cells areosteoblasts and osteoclasts.Osteoblasts build bone materialto make it thicker and strongerat certain sites. Osteoclastsdissolve bone. Together, theyform a team that grows andremodels bones throughout life asyou grow taller, stronger, heavier, and older.

New layers of skin will seal and protect thiswounded area.

Skin,Bones,& more


Tissue engineers can use the osteoblasts to grow newbones. They place these bone-grower cells in a biomate-rial scaffolding with the mineral component of bone. Thecells use this structure for support while they produce theproteins and minerals to grow new bones. Placing growthfactors in key areas of the scaffold helps shape the bonegrowth. In some cases, the scaffold is placed right on thebone defect in the patient, and new bone tissue growsinto the scaffolding.

Tissue engineers hope to be able to design a bone tomatch the shape of an individual patient. Computers willhelp by layering cells and biomaterials in two dimensionsat a time, building towards the complex three dimen-sional structure of a real bone.

Cartilage: Shock AbsorbersMany an athlete has been broughtdown by damaged cartilage.Cartilage is the cushioning tissuein our joints and knuckles, andit gives shape to our nosesand ears. It has a texturelike a cake of dry soap.When lubricated byjoint fluids, it pro-vides a slipperysurface for the bonesin our joints.

Since cartilage does not

require a blood supply, it

can survive on the nutri-

ents from nearby tissues

that have blood supplies

and from joint fluid.

Establishing a blood

supply remains a major

hurdle for engineering

more complex tissues.

When cartilage in a joint is damaged, the bones grindtogether, causing pain and damaging bones. Repairingjoints can restore athletes to the playing fields and keeppeople off crutches and out of wheelchairs.

Such repairs have become fairly common these pastdecades. They help keep people active, but they are notperfect. A standard replacement part is made of metal orplastic molded to the shape of a normal hip joint. This solidmaterial permanently replaces the entire joint. It cannotgrow and remodel itself as the person grows and ages. Afterten or twenty years, it often needs to be replaced again.

Tissue engineers are working to overcome these prob-lems. They are developing a hip replacement using newbiomaterials that can become part of the living, grow-ing, changing body. Itbegins as a porousscaffold with space forthe cartilage cells togrow. These cellsgradually replace thebiomaterial, leaving a“living” joint that cangrow and change alongwith the body.

Another method isalready beingintroduced.Doctors injectcartilage into apatient’sinjured joint.There, thecells rejointhe damagedcartilage andbecomeanchored to thesurroundingtissue.

In the future, doctorswill be able to usecartilage to rebuild abadly injured nose,cheek bone, or jaw.They hope to be ableto inject cartilagetissue with a soft

biomaterial scaffoldthat gels atbody temperature to take a desired shape. Afterseveral months, the cartilage cells will replace

that scaffold, forming a cartilage tissue with thesame contour. Thus, the face will be rebuilt from the

inside, without the pain, expense, and difficulties ofplastic surgery.■

This collagen scaffold molds the shape for anew, cushioning joint.

The bone cells in this biomaterial scaffold willproduce proteins and deposit minerals tomake the bone as good as new.


Heart: Power Supply of the BloodstreamThe heart is an incredibly complex organ. In additionto its four chambers, it has a muscular wall, bloodvessels, an electrical system, and large valves to directthe flow of blood between chambers. Fortunately, whena heart goes bad, we can replace heart valves and bloodvessels, and sometimes the heart itself. However, thesupply of healthy hearts for heart transplants is verylimited, and a patient’s immune system often rejects the“foreign” organ.

Tissue Engineering may eventually overcome problemsof shortage and rejection. Tissue engineers can alreadygrow heart valves using biomaterials and human cells.They are working on ways to grow blood vessels and to

strengthen the heart walls by transferring muscle cellsfrom the limbs to the heart. (See the Profile on page14.) One day they may be able to engineer an entirethree-dimensional heart shaped muscle to replace theheart itself.

Liver: Setting the Body RightPerhaps less famous than the heart, the liver is equallycomplex and vital. It creates proteins, protects againstinfection, removes toxins from the blood, and helpsdigest food. To do all these tasks, it has two bloodsupplies, ductwork for the removal of bile, and a unique

tissue structure that allows it to processbody fluids.

When a liver becomes badly damagedby disease or alcohol abuse, thepatient will die unless a rare livertransplant is available. To helppeople waiting for a transplant,tissue engineers created apartial replacement liver. Thisstructure contains liver tissuein a biomaterial casing.It is attached to a patient’sarteries and veins butremains outside the

Complex OrgansComplex Organs

Constructing a heart requires plumbing (to pump bloodthrough its pipelines), electricity (to wire the electricalimpulses), doors (valves directing blood to differentchambers), frames (muscles, walls, connective tissues),and sheet rock (membranes).



Spare Parts: Who Gets Them?In the future, we may have the technology to make replacement tissues and organsfor any individual. Clearly, these replacement parts could solve many life-threaten-ing medical problems. But, like most scientific advances, these benefits may becomplicated by difficult choices. Here are some of the concerns scientists have:1) Availability: Who will get a replacement part if there are not enough resourcesto make one for everybody who needs one? Will young people be favored overold? People who have taken care of their bodies over people who abused themwith cigarettes and alcohol? Who will set the priorities?2) Cost: Engineered tissues will be expensive. Will only wealthy people be able toafford them? Should health insurance companies cover them for everybody? Willwe 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 cut-off age? Should we keep trying to rebuild worn-out bodies?

body. When the blood flows throughthe device, the liver cells performtheir functionsin cleaning the blood and digestingfood. This device can keep a patientalive until a transplantable liver canbe found.

Creating this artificial liver was madepossible by a breakthrough in cellgrowth technology. Until recently, noone could grow human liver cells in alaboratory culture. Scientists usedcomputers to test all the possiblecombinations of nutrient fluids thatliver cells might need to grow. Thecomputer helped them identify theright mixture for growing liver cells.Tissue engineers can now grow thecells that will eventually be used toengineer a working liver tissue.

Muscles: Moving Through LifeMany diseases such as musculardystrophy cause muscles to degener-ate. In some cases, people losestrength in the large muscles, suchas those that move arms, legs, andthe head. In advanced cases, peoplealso lose the involuntary musclesthat allow them to eat, breathe, anddigest food. They need respiratorsand feeding tubes to survive. Thus,learning to repair and strengthenmuscles could prevent a lot ofhuman misery. Tissue engineers arehoping to do just that.

When muscle cells grow in a labora-tory culture, they join together tobecome fibers. If the culture is“stretched” the way real musclesstretch, these fibers form very thin

THIN

K

ABOUT THIS!!If you could goin for a “tissuetune up” everytwenty years,would you still

try to take careof your body, or

would you just waitfor a tissue “upgrade?”

“Hearts!?? No, No, …We wanted livers!”

muscle-like tissues. Tissue engineerscan coax the muscles to form apredictable structure. To do so, theyuse laser patterning techniquessimilar to those used to make printedcircuit boards for electronics. They“print” a pattern on the biomaterialwhere cells will attach. The patternsimitate the structure of a particulartype of muscle.

The next challenge for tissue engi-neers is to find away to makeblood vessels andnerve cells growinto muscles.Then, thesemuscles may beused to treatparalysis ormuscularweakness.■

These are magnified images of myoblasts patterned on biomaterials.The image on left shows very narrow adhesive lines and the image on right showswider adhesive patterns.

Tah

sin

Ogu

z A

cart

urk

, MD

, Pa

ul

A. D

iMil

la, P

h.D

, an

d P

att

i P

etro

sko,

MS


ParallelTechnologies

To build a house, we have to know how it will lookon 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 tobuild a new tissue: how a real tissue looks insideand out, how it works with other tissues, and how itdevelops and grows.

A Study in TissuesWhen people first studied tissues, they were fascinatedby the differences in texture, color, form, and function.People from the past would be amazed at how completelywe can now “see” tissues. The National Library ofMedicine’s “Visible Human” project shows a slice by sliceview of a body from the inside. (See graphic on page 4.)Each view is digitized on the computer, so scientists canpluck a “virtual” tissue from the body, turn it, and studyits shape, texture, and organization. This ability will helptissue engineers manufacture artificial tissues.

The invention of the microscope allowed people to seethat many individual cells are the building blocks oftissues and to observe how the structure of tissues affectstheir function. Today, new imaging methods provideglimpses of how tissues look in action in living animalsand humans. These images provide the foundation forlearning how to build replacement tissues that willfunction properly in the body.

The relatively new study of genes allows us to understandthe cells within tissues on a genetic level. The interna-tional Human Genome Project has identified many genesresponsible for the structure and function of tissues.Tissue engineers may be able to use this knowledge tochange a diseased tissue by inserting a healthy gene in it,

or to create customized replacement tissues.■



NASA Tissue ResearchIf tissue engineering sounds “spaceage,” consider this. Scientists atNASA are growing tissues bothaboard the Space Shuttle and at theJohnson Space Center in Houston.Why? Because earthbound scientistshave found that, in some situations,gravity interferes with the wayengineered tissues grow in thelaboratory. They do not develop theproper shape of natural tissues.Tissues grown on the Space Shuttle orin the Space Center’s “microgravitybioreactor”— which is an incubatorfor growing cells without the influenceof gravity — have a more naturalstructure. Eventually, these experi-ments may help us learn how todevelop more natural-looking tissuesin our natural gravitational environ-ment. After all, our own tissues grownormally in gravity!▼

Many other technologies also contributeto tissue engineering:

• Microscopic imaging techniques show the structure oftissues at the cellular level;

• Micro-robotics and cell grippers place cells and scaffold-ing together;

• Polymer chemistry develops appropriate materials andstructures for biomaterial scaffolding;

• Computers handle the information needed for tissueengineering;

• Manufacturing helps build biomaterials and incubators(bioreactors) for growing and nurturing tissues.

Thus, many diverse areas contribute to tissue engineeringand offer exciting and valuable career opportunities fortoday’s students and tomorrow’s scientists.

Pennsylvania Biotech Association 13

Technologies Working TogetherGrowing complex tissues involves four impor-tant areas of science and technology: cellbiology, molecular biology, biomaterials science,and computer-assisted design and manufacture.

Cell biology shows us how cells grow and develop toform different tissues. It provides techniques forgrowing cultures of specific cells at specific rates, andknowledge about growth factors and other moleculesthat affect cell growth and activity.

Molecular biology teaches us how genes control celldevelopment and how to control differentiation.

Biomaterials science give us the ability to makesubstitute tissues that can work in harmony with thebody.

Computer-assisted design and manufacturingallows us to control precisely the sequence and

pattern of cell growth to create a 3-D tissue.


Pro

file

:Doris Taylor, AssistantResearch Professor

Doris Taylor runs a laboratory in the Departments ofMedicine and Surgery at Duke University MedicalCenter. She has a B.S. in biology and physicalscience from Mississippi University for Women and aPh.D. in Pharmacology from Southwestern MedicalSchool in Dallas. She did post-doctoral work incardiac (heart) molecular biology at Albert EinsteinCollege of Medicine in New York.

Doris Taylor’s research mayprovide a long-awaited curefor a common type of heart

disease called congestive heartfailure. This heart failure oftenfollows a heart attack, which scien-tists call acute myocardial infarc-tion. Myocardial refers to the muscle(“myo”) of the heart (“cardia”), andinfarction means damage from lackof blood (usually because the arteryis clogged). After a heart attack, thedamaged portion of the heartmuscle dies, and the heart eventu-ally fails. “The heart cannot repairthe damaged muscle because itsmuscle cells cannot reproduce,”Doris explains. “You are born withall the heart cells you will everhave. Your heart grows because thecells become larger, not becausethey multiply.”

However, other muscles do have theability to repair themselves becausethey contain cells called myoblasts,which can reproduce. Myoblasts areimmature tissue-specific stem cellsin muscles that can produce morespecialized muscle cells whenneeded. “We are always damagingour skeletal muscles – the ones thatmove our bones – when we strainthem or bump into things,” Doriscontinues. “When our skeletalmuscles are damaged, they stimu-late the myoblasts to reproduce andmake more muscle cells to repairthe damage.”

Doris asked herself, “Why don’t wetake skeletal myoblasts and see if wecan transplant them into the heartand get them to live there?” Shehoped that the transplanted myo-

blasts might reproduce as they do inskeletal muscles and replace thedamaged heart cells. Her laboratoryexperiments with animals show thatthe myoblasts do seem to help theheart muscle repair itself!

Every year in the United States, abouthalf a million people have heart attacks.Many of them go on to develop heartfailure – a leading cause of death inpeople over 65. Doris envisions thefollowing scenario. “When someonecomes into the emergency room with aheart attack, we take a tiny bit ofmuscle from their arm or leg andextract the myoblast cells. The ERdoctors continue with their usualtreatment, and we take the myoblaststo the lab to grow them in a culture.After a few weeks, when we have10,000,000 or more myoblasts, weimplant them into the patient’s dam-aged heart muscle, and that patient willsoon have a repaired heart instead ofone that is likely to fail again.”

The next area of research is to findways to make the myoblasts moreheart-like. “If we put them in thekind of extracellular matrix found inthe heart, and then stretch them tosimulate a beating heart, perhaps theywill become more heart-like. Forexample, maybe they will form thekind of electrical connections thatother heart cells have. That would beincredibly important!”■



IACTIVITY:ACTIVITY:“Reverse” Tissue Engineering

Strong Bones/Weak BonesYou have probably learned thatcalcium builds strong bones. Yourbones actually start out fairly soft andflexible. The bone tissue developsaround a scaffold made of elasticfibers and collagen, which is the soft,flexible material that also forms thescaffold of cartilage and skin. Asbones develop, the bone cells depositthe mineral calcium in the scaffold.This calcium gives bones morestrength, density, and mass.

Bones are dynamic tissues that arealways losing and gaining calcium.As you grow old, your bones tend to

lose more than they gain. Tokeep your bones strong, youneed to add calcium to yourbones throughout your life.Otherwise, your bones will lose

their density and massbecause they are losing

calcium. This loss ofcalcium causes

broken bones, bentbacks, andshrinking height.Have you everseen a stoopedover old person orsomeone with a“dowager’shump?” Theirvertebrae are sodemineralizedthat they collapse.

In this activity, you will see firsthand what happens when bonesbecome demineralized. To under-stand what happens, you shouldknow that acids can leach (dis-solve) minerals out of other sub-stances. Acid rain can leach mineralnutrients out of soil, and acidicwater can leach dangerous metalssuch as lead and copper out of pipes.In the same way, acids can leachcalcium out of bones.

Materials• Three cooked chicken thigh

bones

• Two 250 mL beakers

• Vinegar

• Distilled water

Procedure1) Examine the thigh bones and

note the different kinds of tissuesyou see. Draw a diagram of thebone and label the tissues.

2) Place a bone in a beaker and pourin vinegar to cover.

3) Place a second bone in a beakerand pour in distilled water.

If you were a tissueengineer, howwould this activityhelp you under-stand what kind ofscaffold you would

need to design toengineer a bone?

What kind of cells would you“plant” in the scaffold?

THIN

K

ABOUT THIS!!4) Allow the bones to soak for

three days.

5) After three days, remove thebones and rinse under runningwater.

6) After the bones have dried, placethem next to the third, untreatedchicken bone. Compare the waythe three bones look and recordyour observations.

7) Now test and compare theflexibility and rigidity of the threebones by trying to bend and twistthem. Record your comparisons.

Conclusions1) Did either of the two liquids affect

the flexibility and strength of thebone?

2) Which of the two liquids do youthink is acidic?

3) Which of the soaked bones showswhat the bone’s scaffold is likebefore it becomes mineralized?

Extensions1) Describe how the bone struc-

tures of a new born baby, ateenager, and an elderly persondiffer.

2) The loss of bone mass in olderadults is called osteoporosis, andit is a major health issue for the

elderly. Find out moreabout why people lose

their bone mass, whatyou can do toprevent it happening

to you, and why youshould start now! ■

VI250 ml

250 ml

125 ml

125 ml


Dear Students:

Biotechnology and the rapid advances of science are in thenews often because they are providing new opportunities forimproving human and animal health, agriculture, and therestoration of damaged environments. This issue of Your World/Our World is designed to allow you to explore how biotechnologywill influence your life and your world by introducing you to thenew area of tissue engineering. Research in this area is underway todiscover how tissues can be restored, maintained, or replaced byengineering or creating new tissues.

We hope that greater understanding of emerging scientific areas willencourage you to continue to study science and mathematics. Wealso welcome your selection of biotechnology as a career and yourparticipation as a co-discover of tomorrow’s science and technology.

Sincerely,

Jeff DavidsonExecutive Director, Pennsylvania Biotechnology Association

PBA would like to acknowledge Pittsburgh Tissue Engineering Initiative, Inc. fortheir 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 thecompanies and organizations listed below. Please join us in thanking them fortheir support:

SponsorsThe Alliance for Science EducationBiotechnology Industry OrganizationCentocor, Inc.Fisher Scientific, Inc.Merck Institute for Science EducationPasteur Mérieux ConnaughtRhône-Poulenc Rorer GencellTosoHaas

Supporting OrganizationsUtah State University Biotechnology CenterMassachusetts Biotechnology CouncilMaryland Bioscience Alliance

References

Websites:Pittsburgh Tissue EngineeringInitiative, 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” videosimulation visit General Electric’sResearch & Development site:Three Dimensional MedicalReconstruction at: http://www.crd.ge.com/esl/cgsp/projects/medical/

Other Issues of YourWorld/Our WorldExploring the Human Genome(Vol. 5, #2):The Human Genome Project

Investigating the Brain (Vol. 6, #1):The structure and function ofthe brain.

Organ Function

Brain Controls sensation,muscles, thought

Heart Pumps bloodthroughout the body

Liver Makes proteins,assists digestion offat, removes toxins

Intestine Digests foodMuscle Moves the bodyBones Supports body

structure, makesblood cells (marrow)

Skin Protects body,provides touchsensation, controlstemperature

Cartilage Forms joints, ears,and nose

biotechnology & you - biotech institute

Documents