Tissue EngineeringA.K.A. regenerative medicineLab tested, Vatican approved

In a nutshell

We Break.Mike Tyson vs. Evander Holyfield: Ear BiteMarty 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

– Unless you run out of yourself to graft

– Rejection isn’t a problem

2. 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

Current therapies

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.

1880 1900 1920 1940 1960 1980 2000 2020

0

1

2

3

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Series1

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.