artificial bio artificial organsbonnardm.free.fr/projets/artificial_organs.pdfdiseased organs a...

Ecole Supérieure d’Ingénieurs de Luminy

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ENGLISH PROJECT

Subject

Artificial &

Bio artificial Organs

CUCURELLA Julien BONNARD Maud

Département Biomédical

Promotion 2008


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Abstract on « Artificial Organs »

During the past three centuries, there have been many advances in medical science.

Before this time, ways of diagnosing and curing sickness were only mythic. When engineers

first started to apply their problem-solving techniques to medical science, the world leaped into

a new age. This brought along the development of the artificial organ. Artificial organs have

prolonged the lifespan of human beings. Organs such as kidneys, heart and skin are needed in

order to survive.

Everyone dreams of a completely implantable artificial heart. We already implant mini

turbines in the heart but it is not possible yet to create an autonomous implantable heart. In

many cases where death would have been imminent, artificial organs have allowed people with

diseased organs a chance of survival. As technology improves, the design of artificial organs

also improves. Nowadays, the main artificial organs which are fast evolving are: kidney,

muscle and pancreas. Indeed, it is now possible to use an artificial kidney on a patient

suffering from a deficiency. The aim of this technology is to perform the task of removing

waste products from the human body until a graft is possible.

Regarding muscles, they are not necessary in order to survive. However, researchers

are trying to repair limb losses with artificial limbs. Their plan is to produce articificial muscles

based on a chimical polymer substance which has the capacity of contracting under the

influence of an electrical or chimical impulse.

They are also working on an implantable artificial pancreas, but probabilities of rejection

are still too high to carry out an experiment on man. Improvement of artificial organs

lengthens the life of an organ disease sufferer.

At the moment, the main obstacles that researchers have to face are biocompatibility and

devices miniaturization...


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Résumé sur « Les organes artificiels »

Au cours des trois derniers siècles, beaucoup d’avancées ont vu le jour dans le domaine

des sciences médicales. Autrefois, les connaissances en matière de diagnostic et de guérison

relevaient du mythe. Lorsque les ingénieurs ont commencé à innover de nouvelles techniques,

le monde est entré dans une ère nouvelle. Les organes artificiels, depuis leur création, ont

permis de prolonger l’espérance de vie des humains. Des organes tels que les reins, le cœur,

et la peau sont indispensable pour survivre.

Nous rêvons tous qu’un cœur artificiel implantable voit le jour mais malheureusement

ce n’est pas encore possible. Dans beaucoup de cas où la mort du patient allait être

imminente, les organes artificiels ont permis de donner une chance de survie. De nos jours, les

principaux organes artificiels ayant un avenir certain sont le rein, le muscle et le pancréas. En

effet, il est désormais possible dans l’attente d’une greffe, d’utiliser un rein artificiel afin de

suppléer les fonctions d’élimination des déchets du corps humain.

En ce qui concerne les muscles, ils ne sont pas nécessaires à la survie du patient.

Cependant, des chercheurs essayent de remplacer des membres perdus par des membres

artificiels. Ils prévoient de réaliser des muscles artificiels basés sur une substance chimique

polymère capable de se contracter sous l’influence d’une impulsion chimique ou électrique.

Ils travaillent également sur un modèle de pancréas totalement implantable, mais les

probabilités de rejet sont encore trop élevées pour qu’un essai de transplantation sur l’homme

soit réalisé.

Aujourd’hui les chercheurs doivent faire face à plusieurs obstacles majeurs à savoir la

biocompatibilité et la miniaturisation des dispositifs.


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Abstract on « Tissue Engineering »

There are several treatment options for organ failure or tissue loss: transplants, reconstructive surgery, artificial prosthesis or mechanical devices (kidney dialyzers, prosthetic hip joints, mechanical heart valves), but unfortunately, they are imperfect. Mechanical devices do not have the capacity to perform all functions of an organ and prosthetic replacements present risks such as thrombosis, an increased susceptibility to infection, limited durability, need for reoperations.

In this context, the emergence of the science called tissue engineering is more than just salutary. The purpose of tissue engineering is to create tissues in culture for use as replacement tissues for damaged body parts. Within the past 10 years, the creation of bio artificial tissues has achieved a series of successes.

Tissue engineering combines principles of medicine, cell and molecular biology, materials science and bioengineering, for the unique goal of generating bio artificial tissues and organs. Skin, cartilage and bone have been synthesized in the laboratory, and success has been predicted in the creation of blood vessels, blood and organs such as heart, lungs, pancreas, and liver. Attempts have been made to create artificial corneas, intestines and heart valves.

However tissue engineering also has its disadvantages. The main difficulties tissue engineering scientists may encounter are related to cell isolation and preparation and to transplantation complexity. The ethical controversies surrounding the harvesting of cells from embryonic sources could be a problem too.

Even so, great progress has been made in tissue engineering research, and greater possibilities have been opened up for the future, including the creation of entire body organs.


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Résumé sur « L’Ingénierie Tissulaire »

Face à un organe défaillant ou à la dégénérescence d’un tissu, plusieurs options sont

envisageables: greffes, chirurgie reconstructrice, prothèses artificielles ou dispositifs

mécaniques (dialyseurs, prothèse de hanche, valves cardiaques mécaniques).

Malheureusement aucun de ces procédés n’est parfait.

Les dispositifs mécaniques ne sont pas suffisamment performants pour remplacer

toutes les fonctions d’un organe et les prothèses artificielles présentent des risques de

thrombose, augmentent le risque infectieux et ont une longévité limitée ce qui nécessite des

ré-opérations.

Dans ce contexte, l’apparition d’une science telle que l’ingénierie tissulaire est plus que

salutaire. Le but de l’ingénierie tissulaire est de remplacer les tissus malades du corps humain

par des tissus sains créés en culture. Ces 10 dernières années, la création de tissus bio-

artificiels a connu une série de succès.

L’ingénierie tissulaire regroupe des principes de médecine, de biologie cellulaire et

moléculaire, de science des matériaux et d’ingénierie biomédicale, dans l’unique but de

générer des tissus et des organes bio-artificiels. De la peau, du cartilage et de l’os ont déjà été

synthétisés en laboratoire. Les chercheurs semblent confiants quant au futur succès de la

création de vaisseaux sanguins, de sang et d’organes tels que le cœur, les poumons, le

pancréas et le foie. Des tentatives ont été menées en ce qui concerne la création de cornée

artificielle, d’intestins et de valves cardiaques.

Cependant, l’ingénierie tissulaire ne présente pas que des avantages. Les principaux

obstacles rencontrés par les scientifiques sont liés à l’isolation et à la préparation des cellules,

ainsi qu’à la complexité des greffes. Il faut également tenir compte des polémiques éthiques

concernant l’utilisation de cellules embryonnaires.

Néanmoins, de gros progrès ont été accomplis dans le domaine de la recherche en

ingénierie tissulaire et des ouvertures vers de plus grandes possibilités semblent se dessiner,

comme par exemple la création d’organes dans leur intégralité.


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Organes artificiels et ingénierie tissulaire Abstract on « Artificial Organs » Abstract on « Tissue Engineering »

I/ Artificial organs 1/ What is it ?

2/ Artificial kidney

a) How does it work ? b) Kidney transplant c) Results

3/ Artificial muscle

a) How does it work ? b) Results

4/ Artificial pancreas

a) The medical equipment approach a.1 How does it work ? a.2 Drawbacks

b) The bio-engeenering approach a.1 How does it work ? a.2 Problems with the bio-artificial pancreas a.3 Design objectives

5/ Conclusion

II/ Tissue Engineering 1/ What is it?

2/ How does it work? a) Stem cells b) Scaffold c) Bioreactor

3/ Applications 4/ Conclusion

Bibliography


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I/ Artificial Organs

1) What is it ?

In medicine, a prosthesis is an artificial extension that replaces a missing body part.

Prostheses are typically used to replace parts lost by injury (traumatic) or missing from birth

(congenital) or to supplement defective body parts.

Within science fiction, and, more recently, within the scientific community, there has been

consideration given to using advanced prostheses to replace healthy body parts with artificial

mechanisms and systems to improve function. Although no such "enhancement prosthetics"

have yet been created and demonstrated to work for healthy individuals, the morality and

desirability of such technologies is debated. Body parts such as legs, arms, hands, feet, and

most other body parts can be replaced.

It is now possible to save more and more patients suffering from diseases or injuries by

replacing defective organs with artificial ones. Researchers are hardly working to find other

kinds of protheses which could bring fantastic possibilities such as artificial eyes or an artificial

heart...

We are going to study three types of artificial organs that could save many lives or at least,

ameliorate patients’ life in the future : artificial kidney, artificial muscle, and artificial pancreas.


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2) Artificial kidney

a) How does it work ?

Artificial kidney has helped to treat fatal kidney failures on many patients and it is continuing

to upgrade with new bioengineering innovations. However, artificial kidney, or dialyzers face

certain obstacles as the technology is expensive and complex. Dialyzers are support systems

which can not take on the task of a human kidney permanently without great cost. However,

dialyzer treatments with kidney transplantation have been very successful in returning a

patient to healthy conditions. Fatal kidney malfunctions, while uncommon, occur mostly in the

people of young age. The kidney removes waste material from the body, and when this is not

achieved properly, the patient develops a kidney failure. In cases where conventional methods

can not treat the malfunction, the patient must go through a series of artificial kidney

treatments. The artificial kidney, or dialyzer, is a life support system designed to remove waste

products from the patients body.

A patient receives artificial kidney treatment for about 12

hours each day, two to three times a week, which will remove

all of the features of kidney failure in one to two months.

Then, the patient awaits kidney transplant from a compatible

donor. This treatment causes major financial problems to

many countries because dialysis is expensive to buy and

maintain.


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The particles are moving randomly. They can pass both ways through the membrane.

However, more particles will meet the membrane on the side with a higher concentration.

Therefore more particles will pass through from this side. This means that there will be a net

flow from the higher concentration to the lower concentration. The dialysis solution contains

water, glucose, salts and various substances at the correct concentration for the body. These

substances diffuse through the membrane and into the blood. So the blood leaving the

machine has all these substances in the same concentration as the dialysis solution. The fresh

dialysis solution does not contain urea - so urea (and other impurities) pass out of the blood.

They are taken away by the flow of dialysis solution. Proteins and blood cells are too big to

pass through the membranes so stay in the blood.

On the left is a simplified diagram of a kidney dialysis

machine.

• a tube connects a person's vein to the dialysis

machine

• inside the machine, blood is pumped through tubes

made from dialysing membranes

• dialysis solution is on the other side of the dialysing

membrane, kept fresh by a constant flow

• blood returns to the person's arm

The dialysing membrane allows small particles to pass

through it. The result is that the concentration of these small

particles will end up being the same on both sides of the

membrane. This is called diffusion. Let's see how it happens.


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Dialyzer uses pure water to remove impurities and waste products within patient's blood

streams. The water used in dialysis must be exceptionally pure, else the impurities in the pure

water will get into patients blood streams, causing greater problems.

b) Kidney transplant

A patient completing the artificial kidney treatment, may receive a kidney from a live donor or

a dead one. The biggest issue in transplantation is compatibility between the donor and the

receiver. Even with many years of experience in kidney transplantation, the issue of

compatibility and rejection of the organ has not been completely resolved. Since the

availability of immunosupressive drugs, the threat of rejection has minimized somewhat, but

with great risk to the patient. In most cases, the donor is a close relative of the patient as

there is greater compatibility and a higher probability of successful Transplant. If a patient

were to receive a graft from a dead cadaver, the kidney will need special treatment as it may

not start to function immediately after the transplantation.

Use of immunosupressive drugs was introduced in the 1960's and have improved greatly over

the years. After transplantation, the patient is put into intensive care in the most isolated room

and given immunosupressive drugs. The drug lowers the possibility of rejection by decreasing

the immune responses of the patient. This will allow easier integration of the graft in the

patient's body. However, lower immune responses means that the patient will be extremely

vulnerable to bacteria and virusses, which greatly increases the risk of infection and other

diseases leading to a complete rejection of the graft, possibly causing permanent harm to the

patient. If a complete rejection was to occur, there will be no choice but to remove the graft

from the patient. However, it is possible for patient to receive a second graft and even a third

one. Once the graft is removed, the patient can be returned to artificial kidney treatments to

await a new donor.


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c) Results

The patient who undergoes a successful transplant can return to normal existance. Although a

light work is preferable, there are no restrictions except that the patient will need to be on

continuous survelience with the outpatient department and continue to take their drugs.

Women can bear children and men can become fathers after transplant. Unfortunately, the

course of event may not always be so happy. However, the mortality rate from kidney failure

and transplant has gone down significantly. Patients have been known to survive more than 25

years after a transplant from a well-matched sibling. Patients receiving organ from an

unrelated cadaver donor have also been known to survive more than 20 years. Now, many

patients with kidney failure stands a reasonable chance at a normal life with artificial kidney

treatments and a well-matched transplant.

3) Artificial muscle

a) How does it work ? Many machines can automate some functions of a human muscle. Recent researches into

polymer based artificial muscles may soon yield organs that work more like real limbs.

Reaserchers are developing artificial muscles from polyacrylonitrile (PAN). They discovered

that PAN is a substance which is a combination of a gel and a plastic. Polyacrylonitrile

drastically contracts when its pH changes. In less than 20 milliseconds, PAN fibres start

contracting. They can decrease their length by 20% in two tenths of a second.

This is about the same speed as a human muscle.

Depending on acidity, the artificial muscle fibres can

contract from one half to one tenth of their original length.

Recent researches state that the fibres are capable of

holding four kilograms per square centimetre. A human

biceps can lift a maximum of just over two kilograms per

square centimetre.

Artificial muscle


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The fibres must be wrapped in latex tubes, so that solutions may be pumped to make them

twitch. A reasercher has also been developing an electronically activated muscle that will not

dry or wear out over time. He has coated a commercially available membrane with platinum.

When electrodes are applied, the muscle contracts.

So far, models that effectively simulate muscle movement have been created. Artificial

muscles have experimentally proven they are capable of moving limbs of a skeleton.

Dielectric elastomers are still at a research level, but they have the potential to be produced at

a low cost. By rolling a tube of a thin film with many layers, larger strains can be achieved.

After a couple of years, dielectric elastomers do not show any sign of degradation.

b) Results The amount of contraction for pH-activated fibers is 50% or greater, and the strength of these

fibers is shown to be comparable to that of human muscle. Despite these attributes, the need

of strong acids and bases for actuation has limited the use of PAN gel fibers as linear actuators

or artificial muscles. Increasing the conductivity by depositing platinum on the fibers or

combining the fibers with graphite fibers has allowed for electrical activation of artificial

muscles containing gel fibers when placed in an electrochemical cell. The electrolysis of water

in such a cell produces hydrogen ions at an artificial muscle anode, thus locally decreasing the

pH and causing the muscle to contract. Reversing the electric field allows the PAN muscle to

elongate. A greater than 40% contraction in artificial muscle length in less than 10 min is

observed when it is placed as an electrode in a 10 mM NaCl electrolyte solution and connected


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to a 10 V power supply. These results indicate potential in developing electrically activated PAN

muscles and linear actuators, which would be much more applicable than chemically activated

muscles.

4) Artificial pancreas The artificial pancreas is a promising technology in development to help diabetic persons

automatically control their blood glucose level by providing the substitute endocrine

functionality of a healthy pancreas.

There are several important exocrine (digestive) and endocrine (hormonal) functions of the

pancreas, but it is the lack of insulin production which is the motivation to develop a

substitute. While the current state of insulin replacement therapy is appreciated for its life-

saving capability, the task of manually managing the blood sugar level with insulin alone is

arduous and inadequate.

The goal of the artificial pancreas is : to improve insulin replacement therapy until glycemic

control is practically normal as evident by the avoidance of the complications of

hyperglycemia, and to ease the burden of therapy for the insulin-dependent.

Different approaches under consideration include : the medical equipment approach (using an

insulin pump under closed loop control using real-time data from a continuous blood glucose

sensor), and the bioengineering approach (the development of a bio-artificial pancreas

consisting of a biocompatible sheet of encapsulated beta cells. When surgically implanted, the

islet sheet will behave as the endocrine pancreas and will be viable for years.).

a) The medical equipment approach

A prototype artificial pancreas for patients with type 1 diabetes is about to undergo its first

major clinical trial. The device could put an end to regular glucose testing and insulin

injections, and could prevent life-threatening irregularities in blood glucose levels, say its

creators. Better control of glucose would mean less hypoglycaemia and hyperglycaemia. That

is the really fundamental benefit, more than convenience.


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a.1) How does it work ?

In type 1 diabetes, insulin-producing cells in the pancreas are killed by the body's own immune

system. Scientists know very little about what triggers that attack.

The prototype system comprises a credit

card-sized glucose sensor, a handheld

computer containing an algorithm that

calculates how much insulin the patient

needs, and an insulin pump. Both the

sensor and the flat pump are worn against

the body and are connected via catheters

that just penetrate the skin.

Glucose sensor

The sensor and pump communicate with the computer using radio signals, meaning no

connecting wires are required. Insulin pumps are already used by some people with diabetes.

But the patients simply press a button for a hit of insulin four times a day. The new artificial

pancreas should allow continuous automatic glucose monitoring and insulin supply.

a.2) Drawbacks

This approach has some drawbacks :

� The implantable sensor is inserted into a neck vein leading to the heart.

� The sensor accurately measures glucose in 95% of cases.

� While implantable insulin pumps work for an average of eight years before they have to

be changed, the sensors stop working after an average of nine months.

� The mathematical programs that calculate just how much insulin should be delivered at

different parts of the day also needs to be refined.


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b) The bio-engeenering approach

b.1) How does it work ?

The bio-artificial pancreas is fabricated from living and nonliving components. The living

component is islets of Langerhans (Cluster of endocrine cells found in the pancreas), which

sense glucose levels and secrete insulin. The nonliving component protects the islets from the

diabetic's body yet permits the islets inside to thrive.

A bio-artificial endocrine pancreas replaces nonfunctioning islets of Langerhans. It responds to

changing blood composition with release of hormones including insulin. A bio-artificial pancreas

is implanted into the peritoneal cavity of the diabetic and contains two to three million cells.

Bio-artificial pancreas designs come in four physical types: hollow fibers, capsules, coatings

and sheets.

As we will see, only coatings or thin sheets have dimensions capable of permitting the islets

inside to function normally.


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Below is a micrograph of the most successful thin coating.


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b.2) Problems with the bio-artificial pancreas

The bio-artificial pancreas is the most promising potential cure for diabetes. But technical

requirements for a bio-artificial pancreas are exacting and have proven very difficult to solve.

The problem has proven intractable because the islets inside most bio-artificial pancreases die

of starvation. Most often the surface of the bio-artificial pancreas provokes a foreign body

response. The resulting immune reaction walls off the device and the islets cannot get

nutrition. Another problem has been that the dimensions of most bio-artificial pancreases do

not permit oxygen to penetrate to the core of the device. Sometimes the process used to make

the device damages or destroys the islets.

c) Design Objectives for bio-artificial pancreas

The essential design objectives required to make the perfect bio-artificial pancreas are : to

keep the islet alive and functionning, prevent destructive host response, and assure practical

surgical implantation.

5) Conclusion

Artificial organs are beginning to save lives and to prolonge the lifespan of humans. Artificial

eyes and heart may arrive soon. But nowadays, artificial organs are still not completly reliable

because of many problems such as biocompatibility and miniaturisation. However, recent

improvements let figure out that researchers may find solutions soon.

In the future, more and more organs failures will certainly be repaired by replacing organs with

artificial ones.


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II/ Tissue Engineering

Many human diseases are due to a cellular degeneration in tissues which we don’t know

how to repair. In some cases, the solution can be an organ transplantation, but organ donors

are rare. Research on cells is advancing knowledge about how an organism develops from a

single cell and how healthy cells replace damaged cells in adult organisms. This promising area

of science is also leading scientists to investigate the possibility of cell-based therapies to treat

diseases.

1) What is it?

Human tissue engineering is a relatively new and exciting medical science area that has

the potential to create living tissues and functional organs. This new research field involves

various aspects of medicine, cell and molecular biology, materials science and engineering.

Its purpose is to regenerate, repair or replace diseased tissues or even a whole organ

by parachuting living cells into damaged or diseased tissues to stimulate their repair and

regeneration.

Tissue engineering, also referred to as “Regenerative Medicine”, would be a new

solution to problems such as organ shortage and biomaterials failures. Moreover, it could in

the future allow a more accurate treatment of tissue and organ diseases by reducing graft

rejection and therefore increasing the quality of life of all patients.

For example, it may provide an efficient solution to the problem of arterial failure which

is usually treated by grafting of an inert prosthesis having only a five to ten year life time.

Current applications of this nascent field of “Regenerative Medicine” include treatment

for skin, cartilage and bone diseases or injuries.

More complex products, such as heart valves, blood vessels, ears or corness, are

already in the pipeline.


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1) How does it work?

Tissue engineering needs 3 major elements to create a tissue or an organ:

a) Stem cells

Tissue engineering solves problems by using living stem cells as engineering materials.

Stem cells are cells that have not yet become fully differentiated (specialised). They

have the capacity both to self-renew (to yield through division cells identical to themselves)

and to differentiate (to generate more specialised cells).

Stem cells are precursors to more specialised cells. Some have the potential to

generate every cell type in the body and consequently may be used to create new tissues and

organs. They can typically be broken into four types:

•••• Embryonic stem cells - Stem cells taken from human embryos

•••• Fetal stem cells- Stem cells taken from aborted fetal tissue

•••• Umbilical stem cells - Stem cells take from umbilical cords

•••• Adult stem cells - Stem cells taken from adult tissue

1) Embryonic stem cells exist in the human embryo for a few weeks after

conception. They have a number of distinctive properties:

• They can live essentially

forever without forming

tumors.

• They can divide unequally.

Instead of forming two

identical daughter cells, the

usual result of cell division,

one daughter cell is more

specialized, while the

second is a stem cell.


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One source for human embryonic stem cell would be to use “spare embryos” (embryos

that are no longer needed for infertility treatment). Another possibility would be to isolate

embryonic stem cells from embryos created for research purpose or embryos created by

somatic nuclear transfer (therapeutic cloning). These latter stem cells would have the

advantage of being immunologically compatible with the patient.

However, embryonic stem cells are hard to control: they may pass through several

intermediate stages before becoming the cell type needed to treat a particular disease.

Furthermore, they are ethically controversial.

2) Foetal stem cells can be derived from aborted foetuses and umbilical cord blood

taken at the time of birth. It is postulated, that embryonic cells are the most promising ones

because they are still young enough to be totipotent.

(Totipotent cells can form any human cell, including the placenta. Pluripotent, or

embryonic, stem cells can form any body tissue except the placenta.).

The other cell types are thought to be more differentiated or pluripotent making them

less capable of generating the natural therapies needed to attack disease. There is a reason to

believe, however, that some fetal cells may also be totipotent.

3) Adult stem cells are partly specialized cells that descended from embryonic stem

cells. Less "eager" to specialize than embryonic stem cells, they may linger in the adult body

for decades, although they may become more scarce with age.

Adult stem cells are already partly specialized what reduces the amount of outside

direction needed to create specialized cells. Moreover, they are flexible: they may form other

tissue types. They have been isolated from certain tissues such as bone marrow, skin and

blood used for transplantation.

One of the constraints for using adult stem cells has been the difficulty in isolating the

cells (you wouldn't want to poke around in someone's brain for neural stem cells) and their

low potential to differentiate into different cell types.

Nevertheless, recent studies have shown that some adult stem cells may have the same

potential to differentiate as embryonic stem cells, at least in some cases.


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View of a colony of undifferentiated human

embryonic stems cells

The embryonic stem cell colonies are the rounded, dense masses of cells.

The flat, elongated cells in between the embryonic stem cell

colonies are fibroblasts that are used as a "feeder layer" on which the embryonic stem cells

are grown.

Derived from human embryonic stem cells

Precursor neural cells grow in a lab dish and generate mature neurons (red) and glial cells (green).


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Different types of cells can be used, they are often categorized by their source:

- Autologous cells are obtained from the same individual to which they will be

reimplanted. These cells are preferred as they avoid an immune response in the

patient after reimplantation and cause no pathogenic transmission problems.

However, there may be problems with using this type of cells, such as

unavailability, in cases of a genetic disease of the patient.

- Allogenic cells come from the body of a donor of the same species.

- Xenogenic cells are those isolated from individuals of another species.

- Syngeneic' or isogenic cells are isolated from genetically identical organisms,

such as twins, clones, or highly inbred research animal models.

b) Scaffold

Three major strategies are used to control the regeneration of three-dimensional

tissues:

- The first is the implantation of an acellular matrix to encourage the formation of

a new tissue. But In vivo studies have shown that it is difficult to encourage cell

migration into the scaffold, resulting in poor tissue formation.

- The second is to encourage the self assembly of cells. Although much effort and

several studies have been made, no functional tissue has yet been regenerated

with this method because of a lack of cohesion between cells, and an inadequate

resulting tissue shape.

In fact, external guides and signals, such as mechanical stress and strain,

are essential to make cells grow into functional three-dimensional implantable

organs, and these guides are difficult to apply on non-supported cells.


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- Finally, the use of a scaffold offers the possibility to tailor the initial properties of

the young and fragile construct at the beginning of the regeneration. This

approach consists of seeding one or more kinds of cells on a scaffold (natural or

polymeric) configured to the appropriate shape.

Scaffold used for heart valves

Scaffold used for neuronal cells


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c) Bioreactor

The construct is then inserted in culture medium, in presence of growth factors, and

submitted to specific intracorporeal conditions in a device called a bioreactor to let cells

colonize the scaffold.

A bioreactor improves cell seeding of 3D scaffolds. It can be defined as a device that

attempts to mimic physiological conditions in order to maintain and encourage tissue

regeneration. Culture parameters such as temperature, pH, biochemical gradients and

mechanical stresses are permanently controlled. The culture medium is continually renewed to

supply gas and nutrients to cells. Every culture condition can be modified to study their

influence on the growth of different tissues.

The scaffold, if biodegradable, will disappear, thus leading to a highly coherent, totally

biological and functional tissue.

Already, resulting regenerated tissues have been successfully implanted in vivo.

Bioreactor diagram


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d) To Resume :

Principle of growth on a Scaffold Template

2) Applications

Stem cells offer the opportunity of transplanting a live source for self-regeneration.

Tissue engineering already has many applications on very diverse part of the body:

Skin

The key applications of tissue engineering have been, firstly, the creation of skin from a

patient's plucked hair. Skin (keratinocyte) stem cells reside in the hair follicle and can be

removed when a hair is plucked. These cells can be cultured to form an epidermal equivalent

of the patients own skin and provides tissue for an autologous graft, bypassing the problem of

rejection. It is presently being studied in clinical trials as an alternative to surgical grafts used

for venous ulcers and burn victims.


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Secondly, living human skin tissue is also used to test skin care, chemical and

pharmaceutical products for all sorts of indications. (ex: L’OREAL)

Heart

Both mechanical and tissue prosthetic heart valves have been created, as well as

tissue-engineered blood vessels without synthetic or exogenous materials. Much research

focuses on the creation of cardiac tissue to replace scar tissue after a myocardial infarction.

Cartilage and Bone

Cartilage tissue for surgical procedures has been developed, and the creation of “bone-

on-demand” is being currently pursued. Scientists are trying to concentrate bone

morphogenetic protein (BMP) complex locally, to stimulate bone formation when and where

needed.

Blood

The growth of blood and blood products in the laboratory will soon supply cells for the

therapy of blood disease such as haemophilia or leukaemia. For example, a bone-marrow

transplant is accomplished by injecting stem cells from a donor into the bloodstream of the

patient. (All blood cells are produced in the bone marrow).


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Brain

Neural stem cells were only until recently thought to be strictly embryonic. Many

findings have proved this incorrect. The identification and localisation of neural stem cells, both

embryonic and adult, has been a major focus of current research. Potential targets of neural

stem cell transplants include stroke, spinal cord injury, and neurodegenerative diseases such

as Parkinson's Disease.

Nerves

Promising artificial nerve grafts are being developed for peripheral nerve regeneration,

as well as nerve guidance channels to bridge the gap between damaged nerve ends.

Lung

Another success has been the creation of a lung bud in culture, up to the stage of

branching morphogenesis. Its successful implantation and growth in-vivo would mean the

elimination of typical organ transplantation problems.

Liver, pancreas or bladder

The development of artificial organs is one of the main focus points for future research.

A good matrix system for the development of an artificial liver is under research. The

transplantation of healthy insulin-secreting islets into the pancreas is used in the treatment of

one of the diabetes types, but researchers are trying to produce genetically engineered cells

that overproduce insulin as well. There is also much future hope about the development of

artificial human thyroid tissues, capable of producing T-cells.

Even treatment of sleep disorders is investigated in tissue engineering; there is hope to

reverse some of the symptoms of narcolepsy by transplantation of engineered cells to replace

missing hypocretin/orexin-producing neurons in the brain.


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Leaders in the field of tissue engineering, such as Joseph Vacanti and Robert Langer,

say that we are only at the beginning of a 30-year process that will lead to the effective repair

and replacement of human organs. Indeed, research in the field has fully indicated that tissue

engineering is able to provide alternatives for improving health and the quality of life.

Given the medical and market potential of this relatively new science, there is ever-

growing interest, both academic and corporate, in its technologies. Therefore, necessity has

arisen that safety and efficacy standards be established, such as quality control and evaluation

standards, regulations regarding the sourcing of cells and tissues, the characterization and

testing of materials, as well as preclinical and clinical evaluation. Cohesive strategies that

should encompass all stem cell research are necessary.


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4) Conclusion

To resume, the science of tissue engineering has its advantages and disadvantages. The

solutions it provides are long-term, much safer than other options and cost-effective as well.

The traditional transplantation complications are minimized, and the donor can be the patient

himself/herself. The need for donor tissue is minimal, and the elimination of

immunosuppression problems is a great advantage. The presence of residual foreign material

is eliminated as well.

But this science is still at an experimental stage and the obstacles or challenges tissue

engineering has to face are related to cell isolation and preparation, to biomaterial design, to

the optimization of nutrient transport and to transplantation complexity. Active seeding

presents some technical difficulties, and there may be obstacles to growing cells in sufficient

quantities, to urging their differentiation into the desired cell type and to ensuring their blood

and nutrient supply after implantation in the body.

The difficulties tissue engineering scientists may encounter include the time necessary

for cells to develop in culture before they can be used, and possible lack of function at the

donor site. The ethical controversies surrounding the harvesting of cells from embryonic

sources should not be overlooked. Another ethical dilemma surrounds therapeutic cloning,

another technique used to produce stem cells that can also be employed towards the

production of clones of beings.

Even so, tissue engineering remains a great hope for medicine progress.

Big steps forward have been made in the field of research, and greater possibilities have been

opened up for the future, including the creation of entire body organs.


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Bibliography

Partie 1:

• www.wikipedia.com

• http://www.alcyone.com/max/links/alife.html

• www.cape.uwaterloo.ca

Partie 2:

• http://www.theses.ulaval.ca/2004/22182/ch02.html#d0e364

• http://ec.europa.eu/research/quality-of-life/stemcells/about_fr.html

• http://cat.inist.fr/?aModele=afficheN&cpsidt=792088

• www.wikipedia.com

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