However, there are a lot of

ethical questions still unan-

swered or even untouched.

Therefore I invite you to dive

into this topic and to discuss

it with your friends and fam-

ily. Think out of the box and

raise your voice if you have

something to say. You will

deal with regenerative medi-

cine once you have become

a doctor and you now have

the chance to shape the fu-

ture it.

Enjoy your enthralling journey

through this special edition

of Euromeds!

Europeanly yours,

Sebastian

Dear reader,

Welcome to the brand-new

special edition of Euromeds

on regenerative medicine!

Although regenerative medi-

cine is one of the hottest

medical topics of the future

for sure, it is unfortunately

relatively neglected in our

current medical education.

Therefore we felt the urgent

need to spread the word of

interested medical students

willing to share their valuable

opinion on certain aspects of

this vast medical field.

Since regenerative medicine

will enable us to create and

grow organs on demand, there

won‟t be a shortage of organs

available for donation any-

more. In addition we will be

able to restore tissue func-

tions damaged by congenital

defects and we might solve

the big problem of organ trans-

plant rejection completely,

because the organ‟s cells

match those of

the patient. To

be precise: Re-

generative

medicine has

the great poten-

tial to start a

new era of

medical treat-

ment.

İ N T R O D U C T İ O N

1 0 / 1 1 F İ R S T E D İ T İ O N

E U R O M E D S

European Medical Students’ Association

OFFICIAL NEWSLETTER

I N T H I S

E D I T I O N

I N T R O D U C T İ O N 1

M E S S A G E F R O M

T H E P R E S İ D E N T

1

S O F A R , W H E R E

A R E W E ?

3

T H E W O N D E R O F

C O R D S T A M

C E L L S

4

R E S U L T S R M S S

2 0 1 0

5

P L A S T İ C

S U R G E R Y

8

E F F E C T S O F

A G E O N T H E

R E G E N E R A T İ V E

R E S P O N S E İ N

S K E L E T A L

M U S C L E S

1 0

D İ R E C T

P R O G R A M M İ N G 1 1

M E S S A G E F R O M T H E P R E S İ D E N T

Dear Reader,

It is my great pleasure to open this

edition of Euromeds and to welcome

you all to the brave new world of

regenerative medicine! A world that

has been a dream and remained a

mist for so long!

But standing on the end of the first

decade of the twenty-first century,

are we finally on a verge of some-

thing?

To answer this we may want to back

up a little... A century or so ago

mankind was fascinated by science

fiction. Back than SF was known for

quite some time... If because of no one

else, then because of a visionary

named Jules Verne that sparked the

imagination of thousands in the late

19th century... But somewhere along

that path another man changed the

course of human kind to a great extent

as well... A brilliant mind named Karel

Čapek, the young Czech writer that in-

vented the word “robot”... Now, it

may not seem all that life-changing

at first, but think about it... The SF

genre of the 20th century was indeed

quite fascinated by robots, androids

and cybernetics... R2-D2 and C-3PO,

Data, Terminator, Transformers and

who could forget Isaac Asimov‟s “I

Robot”?!

But what do robotics have to do with

regenerative medi-

cine?

In reality... Not

much! But cybernet-

ics do indeed!

Think about it... In

the late 20th century

cybernetics has be-

come The Thing!

Everyone was talk-

ing about it, every-

one wanted to know

more about it and

we were amazed by

every single step we

got closer to combining Man with

Machine! M&Ms, please excuse the

pun, became every child‟s desire!

Machines fuelled our imagination,

our technological breakthroughs

and, admittedly, our medical mar-

vels! (Just as they did Marvel Com-

ics.) And I‟m not saying it was a bad

thing! Au contraire! The use of micro-

chips has made patients see again!

The use or cybernetic extremities

has made people walk! The use of

mechanic organs has kept people

alive! Nothing short of miracles of

Biblical proportions!

I mean, think about it for a second...

And now stop thinking about it be-

cause we have let our imagination

run wild with cybernetics for long

enough.

And there IS yet another amazing

field we have ignored for quite

some time...

You are guessing... Regenerative

medicine!

The 20th century has given birth to

yet another amazing field of sci-

ence... Genetics!

And this has, in turn, opened many

doors! One of those lead to tissue

regeneration, organ growth and,

again, miracles of tremendous pro-

portions!

Honestly, is the ability to heal, to

make see and to regenerate not of

miraculous proportions? To us that

conduct it may seem as mere sci-

ence, but to the patient it is nothing

short from a second chance. A new

beginning. A miracle.

And so as we thread into the uncer-

tain waters of scientific puzzles,

ethical dilemmas and unexpected

wonders, we have to ask our-

selves... What does this mean to the

patient?

The answer is, I believe, in the root of

the word... Latin: re-generare; which

loosely translated would be “to beget

anew”, “to create again”, “to give new

life”.

I will not go into technical details, but if

we just let our mind wonder like it did

with mechanics, we quickly see that

the possibilities are endless! And much

more human.

No... Not humane. More

human. More natural. Be-

cause what better eyes

can one see with then

with one‟s own? What

better legs can a man run

on then on his own? What

better smile can a woman

gift to the world then her

own?

I dare say that, while cy-

bernetics remains a valu-

able part of medicine to-

day, regenerative medicine is the fu-

ture. It is an awakening science who‟s

prime days are upon us. It is a dream

that I hope our imagination will create...

Imagine!

Tin Knežević

Page 2 E U R O M E D S

Progress requires so much from

us. The main question is: Should

developments of science have im-

pact on our moral responsibility or

our internal system of values?

If you ask me: I think not. Basic

values should give stability and se-

curity to society, it should be a con-

stant in our lives.

Discussion about using embryonic

stem cells is very animated. From

one hand it can help people (it can

give relief to suffering) which is close

to be called a "miracle". From the

other hand it can make us wonder

what human life is about and what

value it has .

Controversy can arise about the

fact how the material is taken.

Mostly germs are used from in vitro

fertilization which couples didn't use.

Even the fact that the couple have to

give their consensus is unconvinc-

ing.

In vitro fertillisation is becoming

more popular day by day. Material

from each treatment is destroyed.

My question is: Do we have to do

that if we can use it in better bright

way? If it has a place in our reality

why don't use it for our advantage?

From the other side do we have any

rights to treat life like that?

Another question which comes to

my mind is the security of using

these embryonic stem cells. . Nowa-

days both medical and military tech-

nologies are developing increas-

ingly. When something new and an

epoch-making discovery appears on

the market we have to realize that a

black market can elaborate as well..

So how do we guarantee that the

material will be in the right place?

There are really a big amount of

significant issues to deal with but

the facts are: Now we have very

likely opportunities to cure diabetes

type I, Parkinson and Alzheimer dis-

ease, heart disease, sight loss, spi-

nal cord injure. Treatments are in

progress so for sure it won‟t be the

end.

During my medical practice on a

department with patients with dia-

betes I was asking kids what they

wanted the most. The answer was

for 99%: live without diabetes.

I started to wonder. If I would be in

a similar situation or I had sight loss

or I wouldn‟t be able to walk

again...What if... I would be blind the

rest of my life? Would I except a

treatment, whatever that meant?

I am happy I don‟t have to answer

this question, because a lot of ethi-

cal dilemmas arise. However, I think

we have to think of and specify the

border between egoism and utility,

If we make a judgement.

I can give you some examples re-

lated to the subject: beginning of

life. There are different terms defin-

ing when we start to be a human in

full meaning:

a) since conception (Christianity)

b) since 120 days after conception

(Islam)

c) since birth (Judaism)

Therefore an embryo can be defined

as a life or a beginning of it, which in-

stead of being destroyed can be used

in other ways: it can be a second

chance for other human beings, so it

still will be a life only for someone else.

Embryonic stem cells research are

also used in other life categories. Very

important thing is that it is now part of

our reality and it seems to be that the

border of fiction has been overcome.

There are now new developmens like :

Technologies for Non-Medical Purpose

or Growing Semi-Living Structures.

From the source which I found I can

say that developments of science con-

necting embryonic stem cell research

are used to create a new consistent

and changeable reality close to nature.

For example house appear as a dy-

namic depend on human unit which

can adapt to our needs. Can't believe

it?? Check it! I recommend it! (AD, Ar-

chitectural Design, Noeplasmatic De-

sign, Vol 78 No 6, edited by Marco Cruz

& Steve Pike)

Nowadays we are worrying and talk-

ing about how and when we should use

embryonic stem cells. I want to make a

step forward. When we will finally have

the answers for those questions I want

to know for what purpose we could use

embryonic stem cells in normal life? Is

it possible that it could exceed from

personal intervention? What kind of

material would it be?

Joanna Borowska

S O F A R . . . W H E R E A R E W E ?

Page 3 E U R O M E D S

Page 4 E U R O M E D S

T H E W O N D E R S O F C O R D S T E M C E L L S . . .

Few subjects in contemporary medi-

cine have generated more therapeu-

tic potential and ethical debate than

stem cells. The ability of stem cells

to differentiate into various cell

types opens up the possibility of new

treatments for regenerating dam-

aged tissue, even those which can-

not be naturally regenerated by the

body such as the central nervous

system.

So what exactly is so special about

„stem cells‟?

Stem cells are cells which are able

to differentiate into many different

cells types and therefore act as

building blocks of organs, blood and

the immune system.

Bone marrow contains immature

haematopoietic stem cells which can

differentiate into all blood cell line-

ages including white cells, platelets

and red blood cells. Most of the

haematopoietic stem cells are within

the bone marrow but other sources

are found in the bloodstream called

peripheral blood stem cells (PBSC),

and in the umbilical cord. These are

called cord stem cells. These

haematopoietic stem cells can be

transplanted in cancer patients

whose own cells have been de-

stroyed through radiotherapy and/or

chemotherapy treatments. These

treatments target areas of rapidly

producing cells i.e. the cancer cells,

but because bone marrow cells also

have a rapid turnover, these can

also get destroyed and compromise

the patients immune system. By us-

ing either a bone marrow transplant

(BMT) or PBSC method, the stem

cells can be restored 1.

Since the 1980‟s, doctors have suc-

cessfully used cord stem cells to

treat over 80 diseases which would

have previously needed a bone mar-

row transplant including leukemias,

other cancers and blood disorders.

What is better about cord stem

cells?

Cord stem cells are different to other

stem cells as they are biologically

younger which increases their poten-

tial. There is less risk of complica-

tions when used in transplants and

it has also been found that the more

stem cells used, the faster the recov-

ery as there are less complications

1,2. Freezing these cells protects

them from aging and common vi-

ruses which normally impact stem

cells in our bodies, giving them

therapeutic advantage 3.

How does this affect me?

Every day two people miss out on

their transplant 4. This is because

there are not enough stem cells at

present to satisfy the demand. The

chances that you might need stem

cells anytime in your life from birth

until the age of 70 is 1 in 217 5. By

donating stem cells from the umbili-

cal cord and placenta after a baby‟s

birth could save lives.

In the UK last year, 80% of all cord

stem units were imported from over-

seas from countries like Spain,

France, Germany, Italy, the USA and

others where there are government

supported national collection pro-

grammes. 65,000 litres of cord

blood were discarded in the UK fol-

lowing births 6 and this is probably

due to the lack of awareness and

education of the benefits of cord

stem cell donation. The Anthony

Nolan Trust has established its own

Cord Blood programme at King's

College Hospital in London and the

Leicester Royal Infirmary and Leices-

ter General Hospital.

Image from www.cordbloodfreezing.com

How are they collected?

If a mother wishes to donate stem

cells, then they must contact the

cord blood bank before the baby‟s

birth. After the baby is born, cord

stem cells are collected from the

umbilical cord and placenta. They

are then processed and frozen for

storage, at temperatures below -

190°C 7. They can be stored indefi-

nitely under the right conditions 8

and can be used by the child, an-

other family member or someone

from the public with who is Human

Leukocyte Antigen (HLA) matched.

The process poses minimal health

risk to the mother or the child and

the advantage of them is that they

are available immediately 9.

The future…

Today, doctors and physicians alike

are pushing the boundaries in regen-

erative therapies using cord stem

cell to offer a real chance for organ

transplantation. With pioneering new

research, the potential for cord

blood for use to induce healing or

repair tissues has led to experimen-

tal therapies to treat cerebral palsy,

brain injury, and juvenile diabetes 10. It is now estimated that „as

many as 1 in 3 individuals could

benefit over their lifetime from the

applications of regenerative medi-

c ine ‟ 1 1 .

Kavita Aggarwal

Imperial College London School of

Medicine

Year 4

References:

1. Lichtenstein P, Holm N, Verkasalo P, et al. Environ-mental and heritable factors in the causation of cancer-Analyses of cohorts of twins from Sweden, Denmark, and

Finland. N Engl J Med. 2000; 343(2):78-85. http://www.nejm.org/doi/full/10.1056/NEJM200007133430201, (accessed 1 September 2010)

2. Rocha V, Wagner JE, Jr., Sobocinski KA, et al. Graft-versus-host disease in children who have received a cord

-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Trans-plant Registry Working Committee on Alternative Donor

and Stem Cell Sources. N Engl J Med. 2000;342(25):1846-1854. http://www.nejm.org/doi/full/10.1056/NEJM200006223422501 (accessed 4 September 2010)

3. Behzad-Behbahani A, Pouransari R, Tabei SZ, et al. Risk of viral transmission via bone marrow progenitor cells versus umbilical cord blood hematopoietic stem cells

in bone marrow transplantation. Transplantation Procee-dings. 2005;37(7):3211-3212. http://www.transplantation-proceedings.org/article/S0041-1345

(05)00750-5/abstract

(accessed 7 September 2010)

4. Anthony Nolan Trust Cord Blood http://

www.anthonynolan.org/What-we-do/How-we-help/Cord-blood.aspx (accessed 14 September 2010)

5. Nietfeld JJ, Pasquini MC, Logan BR, Verter F, Horowitz MM. Lifetime probabilities of hematopoietic stem cell transplantation in the U.S. Biol Blood Marrow Transplant. 2008;14(3):316-322. doi: 10.1016/j.bbmt.2007.12.493. (accessed 7 September 2010)

6. Anthony Nolan Trust Why Cord Blood Saves Lives http://www.anthonynolan.org/What-you-can-do/Save-a-life/Donate-your-umbilical-cord/Why-cord-blood-saves-lives.aspx (accessed 12 September 2010)

7. Kings College Hospital Dual role stem cell bank “poised to save thousands” http://www.kch.nhs.uk/news/archive/2008/dual-role-stem-cell-bank-poised-to-save-thousands/(accessed 7 September 2010)

8. Linden JV, Preti RA, Dracker R. New York state guidelines for cord blood banking. Journal of Hematotherapy. 1997;6:535-41. http://www.ncbi.nlm.nih.gov/pubmed/9483188 (accessed

12 September 2010)

9. National Cancer Institute Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation http://www.cancer.gov/cancertopics/factsheet/Therapy/bone-marrow-transplant

(accessed 1 September 2010)

10. The National Institutes of Health resource for stem cell research What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized? http://stemcells.nih.gov/info/basics/basics6.asp (accessed 7 September 2010)

11. Harris DT, et al. (2007). "The potential of cord blood stem cells for use in regenerative medicine.". Expert Opin. Biol. Ther. 7 (9): 1311–1322. doi:10.1517/14712598.7.9.1311.

(accessed 4 September 2010)

Page 5 E U R O M E D S

R E S U L T S R E G E N E R A T İ V E M E D İ C İ N E S U M M E R S C H O O L 2 0 1 0

A T H E N S , G R E E C E

Haematopoietic Stem Cell

Transplantation: Superman in

the Land of Haematological

Disorders [RMSS - 2nd place]

Mircea-Andrei Sandu 1, Juanita Lestari2

1Carol Davila University of Medicine and

Pharmacy, Romania, 2University of New

South Wales, Australia

Introduction Haematopoietic Stem Cell

Transplantation (HST) is un-

doubtedly one of the major

medical advances in the 20th

century. This article is going to

describe HST and its applica-

tion in haematological disor-

ders. Acute Lymphoblastic Leu-

kemia and Thalassemia, exam-

ples of haematological malig-

nancies and haemaglobi-

nopathies respectively, are go-

ing to be used to illustrate how

HST significantly alter the sur-

vival rate of pa-

tients with haema-

tological disorders.

The shortcomings

and future direc-

tions of HST are

explained at the

end of the article.

HSC Transplantation Haematopoietic

Stem Cell Trans-

plantation (HST) started in 1959

when a patient with leukemia

was treated with total body irra-

diation followed by infusion of his

identical twins‟ bone marrow

(Copeland, 2006). HST is a term

which is used to replace the term

“bone marrow transplantation”

since haematopoietic stem cells

(HSC) can now be harvested

from sites other than bone mar-

row. Examples of these new

sources of HSC are peripheral

blood, umbilical blood and repro-

gramming of somatic cells into

cells which resemble stem cells.

The main underlying mechanism

of HST is replacement of abnor-

mal cells, both malignant and

non-malignant ones with normal

donor cells. (Appelbaum, 2008;

Samavedi& Sahel, 2010). Dis-

eases which are treated with

HST are listed in table one be-

low.

Conclusion

HST has lowered the mortality rate and

increased the free event survival rate for

individuals with haematological disorders

such as ALL and Thalassemia. Just as

Superman is weak against kryptonites,

HST is also faced with problems such as

GVHD, engraftment failure and low effi-

cacy rate in adult patients. With advance-

ment in gene therapy and bimolecular

technology especially in reprogramming of

somatic cells into stem cells look-alike, we

can hope that these problems will be

eradicated in the future.

[….]

To read the full article go to: http://

rmss.athens.helmsic.gr/

participants_assignments/Applications in Hae-

matology.pdf

Epithelial to mesenchymal

Transformation [RMSS - 3rd

place]

Apostolos Vrettos1, Charikleia

Papandreou1

1National and Kapodistrian Uni-

versity of Athens, Greece

More than 100 years ago

Santiago Ramon y Cajal drew

and described the morphologi-

cal appearance of breast carci-

noma so accurately that we

can find what we believe to be

the first description of EMT.

Betty Hay was the first to coin

the term „epithelial to mesen-

chymal transformation‟ in em-

bryos (Hay, 1968), as well as

later describing this cellular

behaviour during migration

(Hay, 1990) and the impor-

tance of the transient nature of

this process (Hay, 1991).

Since then, EMTs have been an

area of interest for many scien-

tists and it is now clear that

they occur in three distinct bio-

logical settings. While the out-

come is the generation of mo-

tile cells of mesenchymal phe-

notype, the mechanisms of

EMT induction and progression

vary dramatically from one set-

ting to another. Future re-

search will surely focus on un-

covering the molecular similari-

ties and differences among the

EMT programs that occur in the

three distinct settings.

Recent independent studies by

Li et al. (2010) and Samavarchi-

Tehrani et al. (2010) in Cell Stem

Cell suggest that a mesenchymal

-to-epithelial transition is a criti-

cal initiating event during the

derivation of induced pluripotent

stem cells (iPSCs) from fibro-

blasts, indicating remarkable

similarities between cellular re-

programming, development, and

cancer. At the transcriptional

level, Sox2/Oct4 suppress the

EMT mediator Snail, c-Myc down-

regulates TGF-β1 and TGF-β re-

ceptor 2, and Klf4 induces

epithelial genes including E-

cadherin. Blocking MET impairs

the reprogramming of fibroblasts

whereas preventing EMT in

epithelial cells cultured with se-

rum can produce iPSCs without

Klf4 and c-Myc. This work not

only establishes MET as a key

cellular mechanism toward in-

duced pluripotency, but also

demonstrates iPSC generation

as a cooperative process be-

tween the defined factors and

the extracellular milieu.

EMT research in the next few

years promises to be exciting, as

new mouse models and molecu-

lar probes are identified to ad-

dress still-unanswered ques-

tions.

[….]

To read the full article go to:

Page 6 E U R O M E D S

http://rmss.athens.helmsic.gr/

participants_assignments/Epithelial to mesen-

chymal transformation.pdf

The recent advances in Cardio-

vascular Medicine – The Re-

generative Medicine way

[RMSS – 1st place]

Amit Tripathy1, Eirini Tsiam-

pousi2

1Sambalpur University, India,

2Ioannina University, Greece

The Romeo and Juliet saga had

its foundation from a very inte-

gral, indispensible, incompara-

ble part of our body which is

now surrounded by the perin-

neal garbage that smells foul

from a majority of households

from the world- “The Heart”.

With the missiles of chemother-

apy, it has been possible to put

the damage caused to be in con-

trol. However, reverting the dam-

aged heart back to normal has

been a nightmare for scientists

throughout the world. May it be

a mighty valve prolapse or vege-

tations in the valve, may it be

con-

genital

heart

defects

or is-

chaemic cardiomyopathy, may

it be peripheral vascular dis-

eases or defects in the conduc-

tion system, the heart has al-

ways been in a constant threat

with a long hunt of searching,

which is now coming to an end

with the advent of almost a

decade of research- “The Re-

generative Medicine”. Regen-

erative medicine is the future

of cardiovascular medicines

which not only ensures care

but also ensures that the heart

becomes perfectly 100% func-

tional. The viability, the practi-

cability, the efficacy and the

reproducibility of the stem cells

was the cause which led to Dr.

Martin Evans winning the No-

bel Prize in 2007.

Regenerative Medicine and

Myocardial Infraction

Myocardial infarction has since

ages been a disease of the

masses especially of the devel-

oped world with an incidence

of 17,600,000 cases of coro-

nary heart diseases from the

United States itself with

8,500,000 being those suffer-

ing from myocardial infarction.

It was even reported that car-

diovascular diseases claimed

151,000 Americans under the

age of 65. The conventional

treatment to this disease which

presents as an acute attack

often cognomened as “THE

HEART ATTACK” accompanied

by angina pectoris was until the

past decade based on pharma-

cotherapeutics with drugs like

diuretics, beta blockers, angio-

tensin converting enzyme inhibi-

tors, angiotensin receptor block-

ers, calcium channel blockers

etc. Regenerative medicine is

the voice of the decade and the

panacea for the future. It is one

of the most efficacious, most

promising gifts to the world of

medicine which has its advan-

tages burying the disadvantages

of the commonly used drugs. Its

disadvantages are the stimulat-

ing factor for which extensive

research is being undertaken in

animal models like primates,

mouse, rat, albino rabbit, swine

etc. so as to nullify the disadvan-

tages.

Regenerative Medicine and the

valves of heart

An estimated 275,000 patients

worldwide undergo heart valve

replacement surgery each year

because of valve abnormalities

they present due to a variety of

pathological causes (eg infec-

tions,prolapse) that can result in

stenosis and regurgitation. Ei-

ther process burdens the heart

and can cause heart failure. [….]

Many scientific teams work on

development of heart valves us-

Page 7 E U R O M E D S

Page 8 E U R O M E D S

Plastic Surgery: Where are we

heading…

Interview with H.A.H. Winters,

MD, PhD, Plastic Surgeon, VU

Medical Center, Amsterdam, the

Netherlands

Which aspects do you like most

of plastic surgery?

What I like mainly is the beauty of

the specialization, that you work

throughout the whole body. We

work with skin, muscles, ten-

dons,bone and fat. We operate

various body parts: hands, feet,

arms, legs, trunk, breasts, the

face. We are concerned with form

and shape of course but also to a

large extent with the function of

various structures

Were you also interested in this

specialization during medical

school?

The idea of working anatomically

was appealing to me at the mo-

ment I started my study. This is

very typical for plastic surgery. We

know more about anatomy and

especially applied anatomy than

other specializations. We don‟t

only know the location of a struc-

ture, but also the function and

the proportions. To be a good

plastic surgeon you have to be

creative and able to think in 3

dimensions. My personal inter-

est is mainly reconstructive

surgery. Most of all repairing

defects of the bone. I thor-

oughly enjoy finding a solution

to a difficult problem.

What are your expectations of

upcoming developments within

50 years from now?

We ARE developers. A field that

knows a tremendous innova-

tion. Everybody is expecting a

lot of the possibilities of regen-

eration, controlling stem cells

to create specific tissue. Theo-

retically more is possible than

in practice. There will be more

focus on this development in

the future. Can we make a kid-

ney out of stemcells from the

abdominal wall? This is where

science wants to be heading.

How far we are now? Not even

close…

It is an extremely difficult job to

make even cartilage, despite

the massive amount of re-

search that has been put into

this for the last two decades.

There is much demand for car-

tilage, because cartilage wear

is a serious and common prob-

lem as we age. Actually, the hu-

man body is build to last approxi-

mately 45 years, then it starts to

wear down and fall apart. We are

getting twice as old with all the

consequences. Imagine, some-

thing could be injected into the

hip, which would create new carti-

lage, or you could place a matrix

at a damaged jaw (or any other

bone), which would transform

into human bone. These would be

major achievements! But I can

not say whether it ever will hap-

pen.

In case you would be wrong, will

plastic surgeons be unnecessary

in the future?

No, because IF you could make

the material. Then the material

would still have to be moved from

the laboratory to the human body.

Here a reconstructive surgeon

would nevertheless be required.

If only to connect the blood sup-

ply to the new tissue. Also plastic

surgery is much more than only

putting in replacement tissue.

What do you think of the growing

emphasis on cosmetic surgery

Obviously cosmetic (or aesthetic)

P L A S T İ C S U R G E R Y : W H E R E A R E W E H E A D İ N G . . . .

ing the technology of stem cells

(Mesenchymal Stem Cells-MSCs ,

Multipoten Adult Stem Cells-

MASCs, Progenitor Cells, Cardiac

Stem Cells-CardiacSCs, Hemato-

poietic Stem Cells-HSCs etc.).

Scientists usually use umbilical

cord derived stem cells, be-

cause they are easy to collect

and less prone to be rejected

by the human organism.

[….]To read the full article go to:

http://rmss.athens.helmsic.gr/

participants_assignments/Applications in car-

diovascular medicine.pdf

surgery is a part of my profes-

sion, but definitely not the only

aspect of plastic surgery. Never

the less, most media attention

goes to cosmetic surgery, be-

cause of the treatment of celebs

etc. This creates the image that

cosmetic surgery and plastic

surgery are the same thing and

that anything goes, as long as

you pay for it. This is a deformed

image and does not do justice to

the majority of plastic surgeons,

who are serious doctors that are

considerate about their patients

wellbeing and do not go by the

principle of:‟Whatever you say,

as long as you pay‟.

Plastic surgeons should provide

good information about the risks

and disadvantages of the de-

sired procedure. In many cases

the patient should be given time

to think it over. Then, if the pa-

tient still wants the procedure

done, after proper information

and advice, the plastic surgeon

should perform the operation

as safe and sound as possi-

ble.

In cosmetic medicine, patients

often don‟t look for glamorous

operations. They just want to

look normal. Someone with a

crooked nose can be very in-

secure and socially isolated.

You can send this person to

the psychiatrist for ten years,

you can also send her to a

plastic surgeon once. The

businessman with bags under

his eyes, tells me that clients

are taking him less seriously.

„They think I have spent the

whole evening in the pub, while

I went to bed at eleven o‟ clock.

„These people are very happy

that a „çosmetic‟ procedure

can make them look normal

and improve their quality of

life.‟

Also, it is just impossible to

draw a line between cosmetic

and reconstructive surgery.

There is a huge gray area. I'll

give you an example. You have

two ladies. Two young women

aged 35. Mrs. 1 has had breast

cancer and would like to have

a reconstruction of the ampu-

tated breast. Mrs.2 has seen

her breasts turn into teabags

after breastfeeding two chil-

dren. Both women feel inse-

cure and want to have their

femininity and self esteem re-

stored. How big is the differ-

ence? Very small! So why do we

talk about a necessary recon-

struction in the first case and

about an unnecessary cosmetic

procedure in the second case.

Why should we assume that the

concerns of the second woman

are rubbish?

I think these examples clearly

show that reconstructive, cos-

metetic and plastic surgery call

for a more nuanced view then

generally provided by the media.

What do you think of face trans-

plants, is it responsible?

I think it's an intervention with a

big risk of long term complica-

tions. The skin has an important

function in the immune system

and has many antigens. There-

fore, after a face transplant, pa-

tients must take potentially dan-

gerous medication their whole

life. Out of ten face transplants

performed in the last 5 years,

two patients deceased because

Page 9 E U R O M E D S

Page 10 E U R O M E D S

of the medication. In addition, if

you look at kidney transplants,

there is a 25-30% chance that

the transplant will be rejected

within the first 5 years. This

might also be true for face trans-

plants! A rejected kidney can be

removed and dialysis can again

take over the kidney function

until a new donor has been

found. But, what do you do when

your face falls off…How do you

find a new donor within a few

weeks time? What do you do in

the meantime? Even though it

would be possible for me to

perform this surgery,.

I feel we should not think about

this too lightly. I know a few

doctors who performed this

surgery, but I find it has a lot of

concerns that go beyond the

technical challenge.

Finally, when are you suitable

as a plastic surgeon?

Specifically you need a good 3-

dimensional insight and fine mo-

tor skills. You also need to be

creative. A part of this you can

learn, a part you can‟t. And of

course, as a plastic surgeon you

need an extensive knowledge

about vascular and functional

anatomy of the human body.

Micky Las van Bennekom

Fernando Leiva Cepas 1

1 Department of Morphological

Sciences (Histology Teaching

Unit), Faculty of Medicine. Uni-

versity Of Cordoba, Spain.

Introduction

Aging is one of the major factors

that transcendence is in the re-

generative response, our goal is

to see how this response varies

with two experimental models

used for muscle regeneration.

Skeletal muscle is an organ of

the body better prepared to pro-

vide answers to injury, this re-

sponse is directly dependent on

satellite cells in skeletal muscle

which make the factors in-

volved, from growth to immune

factors. This is shown in the sat-

ellite cell activation after injury,

which has an extraordinary ca-

pacity to generate genome. Any

changes new fibers through

fudión quiescent myogenic pre-

cursors that are stimulated

work injury or traumatic as

toxic.

This capability is known for

some time, but progress in the

population demographics pre-

sent an increased interest in

understanding the effects of

age on the regenerative capac-

ity of normal in muscle and

their possible profits esqulético

for regeneration in people with

severe atrophy .

Sarcopenia is responsible for

this phenomenon, as can be

evidenced with the passage of

time reduces the number of sar-

comeres present in skeletal

muscle, thus affecting its mus-

cle volume and mechanical

strength.

In the laboratory has been dem-

onstrated by two experimental

models (one controlled and two

uncontrolled) that regeneration

is less cuantitava and qualita-

tively. The first experimental

model, is based on producing

mepivacaine intruducción intra-

muscular injury and subsequent

regeneration to normal

(controlled experiment), as has

been demonstrated in mice over

12 months, the regenerative

response is slower, the number

activated satellite cells is lower

and the number of fibers as

well, this is based on the onset

of sarcopenia suffering every

E F F E C T S O F A G E O N T H E R E G E N E R A T İ V E R E S P O N S E İ N S K E L E T A L

M U S C L E S

Page 11 E U R O M E D S

living thing, and the reduced ca-

pacity of satellite cells to re-

spond to the injury.

Uncontrolled experimental

model has two procedures. The

first consists in the transplanta-

tion of adipose tissue in an area

where there used skeletal mus-

cle. In normal individuals, this

action involves formation of re-

generating fibers from mesen-

chymal stem cells present in the

transplanted adipose tissue, but

in Wistar rats over 12 months

showed that there is less inflam-

mation, less training of muscle

fibers, as well as effects of the

absence of muscular tension

(rajamientos muscle hypertro-

phy and atrophy, endomysial

fibrosis ...). The second proce-

dure is related to uncontrolled

reconstruction of skeletal mus-

cle from an array descelulari-

zada, which has been im-

planted in a muscle which has

ela s injury, thus the regenera-

tive capacity of injured muscle

will be transferred to the matrix

that serves as scaffold for mus-

cle rebuilding.

Conclusions

1. Aging is part of the biology of

normal muscle cell.

2. Sarcopenia is a factor in-

volved in the absence of normal

regeneration, both in vivo and in

vitro.

3. With age, the stem cells of

skeletal muscle satellite cells,

decrease their activity by pre-

venting proper reparative tissue

repair.

4. Experimental models have

confirmed these facts and serve

as examples for the study of

these phenomena and their pos-

sible therapeutic targets.

D İ R E C T P R O G R A M M İ N G — T H E P O S S İ B L E F U T U R E O F R E G E R A T İ V E

M E D İ C İ N E

Interesting, fascinating, new

possibilities, higher aims…only

few, out of who knows how

many attributes that describe a

science with one major subject

of research...improvement of

human health. From the begin-

ning of its existence, the medi-

cal science differed a lot from all

other scientific fields. Its unique-

ness proved to be well deserved

having in mind the fact that peo-

ple nowadays have the opportu-

nity of having longer, healthier

and happier life and the one to

blame is this specific field of hu-

man interest. Having its roots in

the time of Hippocrates, medical

science was always trying to

reach higher aims bravely con-

fronting the health problems

arising during human exis-

tence. The results we have now

are priceless. But still, there

are too many medical myster-

ies that need to be solved. Re-

generative medicine was al-

ways one of them. However, it

definitely won‟t remain un-

solved forever.

Can you imagine the possibility

of being able to directly turn

one type of cell into another,

more required in a certain

situation? Having that kind of

opportunity the cells which are

not necessary for the survival

of a person can turn into a so-

lution of his/her life threatening

situation, eliminating the donor-

compatibility problems. The very

thought of that makes me feel

challenged to continue writing

and researching.

The scientists have had this idea

in mind for 10 years until now.

In the early period of their re-

search, they were trying to get

the specific type of cell the pa-

tient needed by firstly generat-

ing a pluripotent stem cell from

the less needed cell type and

afterwards turning it into the cell

type desired. They succeeded to

do this by using transcription

factors determinating a stem

cell level and introducing their

Page 12 E U R O M E D S

genetic material to the cell being

transformed, by transduction.

This “prephase” of the cell type

was called induced pluripotent

stem cell (iPSC) and was accom-

plished for the first time in Ja-

pan in 2006. Nevertheless too

many problems arised from this

artificially made stem cell.

Among them, one of the most

serious proved to be the fact

that some of them can develop

inappropriately to form tumors.

The problems did not entail de-

termination of the scientific

work. On the contrary, they chal-

lenged the scientists to continue

exploring. Soon afterwards they

realized that there is a possibil-

ity of directly turning one type of

cell into another skipping the

iPSC state. The process was

called direct reprogramming and

was also done by transduction,

after the specific transcription

factors for the cells needed

were discovered. There have

been reported two degrees of

the process:

- transdetermination - dediffer-

entiation of progenitor cells

(cells that appear to be com-

mitted to their fate, but not yet

fully differentiated) into differ-

ent cell type;

- transdifferentiation - dediffer-

entiation of a fully differenti-

ated call into a different cell

type;

Over the last period much pro-

gress has been made in this

field in order to make any cell

type into a muscle cell, blood

cell or neuron. The results are

fascinating.

One of the things that

intrigued me the most was the

possible usage of this process

in cardiological patients having

largely damaged heart muscle,

as a result of several heart at-

tacks. Recently it was pub-

lished that the scientists at the

Gladstone Institute of Cardio-

vascular Disease in San Fran-

cisco have found new way to

make beating heart cells from

the cardiac fibroblasts. They

discovered that a combination

of just three of the 14

transcription factors im-

portant for formation of

the cardiomyocytes

(Gata4, Mef2c and

Tbx5), was enough to

efficiently convert fibro-

blasts into beating cells.

Considering the fact that

half of the cells in the

heart are fibroblasts, this

sounds very promising in context

of the future cardiac regenera-

tion.

However all the research

done so far was part of animal

studies. Its idea and therapeutic

implications are fascinating but

the process has to continue and

reach higher goals. It must incor-

porate human cells, before it

can be clinically used. The us-

age of it regularly in the clinical

practice will open a new chapter

in the priceless book of regen-

erative medicine. It will let the

people in need, to have opportu-

nity to continue living a normal

life. This sounds quite motivat-

ing not only for the researchers

but for the students as well,

don‟t you think?

In order to make things

clearer, one of the most re-

spected professors and at the

same time scientists in our

country, Prof. Dr. Mirko Spiroski,

head of the Institute of Immuno-

biology and Human Genetics in

Skopje was pleased to share his

personal, professional opinion,

considering the topic.

1. What kind of thoughts and

perspectives do You have, con-

sidering the usage of the direct

reprogramming as a process

with the purpose of improving

the regenerative medicine?

Direct reprogramming of the

cells in the medicine is one of

the therapeutic approaches for

very serious and often fatal dis-

eases. Theoretically it is possible

to reprogram each cell in the

human body, but practically

some of the cells are not possi-

ble to be reprogrammed (e.g.

cells of CNS), others are very

heterogeneous (e.g. immune

cells) and are developed during

the growth of the healthy organ-

ism. Many cells are communi-

cating between them and/or

with other cells with special

molecules which depend of the

developmental stage of the cells

and interaction with other mole-

cules. All cells are equipped with

very different signalling path-

ways for different functions. We

should be very careful in the

case of introducing regenerative

tissues and/or cells in the living

human organism and investi-

gate all of these and other as-

pects before final acceptance of

reprogrammed cells for healing.

2. Do You think that the

introducing of the transcription

factors in the human cells would

be equally successful as the

same thing done in the mice

cells?

Human cells are more complex

and need more investigations

and transcription factors for re-

generation. We know most of

these interactions and I expect

in the very near future conclu-

sive results with the human

cells.

3. Have You ever been part of a

scientific research work con-

nected with the topic and if so

would You please like to share

with us Your personal experi-

ence?

Unfortunately, I was not in-

volved directly in any project

about the regenerative medi-

cine because in the Republic of

Macedonia we do not have fa-

cilities and financial support for

scientific investigation of this

field. But, we organized Mace-

donian Bone Marrow Donor

Registry (www.mkdr.org.mk/

mkbmdr) as a first step in pre-

paring biomedical background

for the future investigations of

regenerative medicine and we

are preparing our staff with fa-

cilities and knowledge to start

investigations in the near fu-

ture.

4. Do You think that there

could be a possibility, the

fibrous tissue generated in the

healing process, during the

recovery of a myocardial

infarction, to be directly

reprogrammed into heart

beating cardiomyocytes?

It is hard to believe that fibrous

tissue generated in the healing

process can be reprogrammed

into heart beating cardiomyo-

cytes, but other models of

treatment of stem cells before

and/or after injection into hu-

man heart should be successful.

5. Last but not the least, what

are Your predictions considering

the process on local, as well as

on international level, in the fu-

ture? Are there any other possi-

bilities where it can be used,

besides the regenerative medi-

cine as a primary aim?

Regenerative medicine in the

future in the developed coun-

tries, especially in the European

Union, USA, China, Japan and

similar countries, will be applied

in almost all the fields of medi-

cine and the limits will be tech-

nological and ethical issues. In

the developing countries the ap-

plications will be slower and

later than in developing coun-

tries, but the differences will be

increasingly reduced. Special

role in the development of re-

generative medicine should be

delegated to small and medium

private enterprises as a flexible

and fast biomedical producer.

Verce Stankovic

Page 13 E U R O M E D S

EMSA – c/o Standing Committee of

European Doctors (CPME) – Rue

Guimard 15 – B1040 Brussels -

Belgium

Web: www.emsa-europe.org

E-Mail: eeb@emsa-europe.org

WHAT IS EMSA?

The European Medical Students‟ Association (EMSA) was founded in

Brussels in 1991. It integrates medical students in geographical Europe

through activities organised for and by medical students and representing

them in Brussels. Faculties are members, not the individual countries. Since

EMSA‟s foundation many medical faculties throughout Europe enrolled with

EMSA. It currently units 50 medical faculties from countries across Europe.

EMSA seeks to improve the health and the quality of care of the citizens of

Europe by acting as a conduit for increased interaction and sharing of

knowledge between European medical students in the areas of medical education,

ethics and science.

E U R O P E A N M E D İ C A L

S T U D E N T S ’ A S S O C I A T I O N

Thank you for reading this special edition of Euromeds “Regenerative Medicine”.

We really enjoyed working on an edition about a field of medicine with so much innovation

and yet so much unfamiliarity. We hope we have given you an idea about the infinite and

miraculous possibilities of this field in the future, but also about the ethical discussion which

might arise.

Above all we would like to thank Joanna, Verce, Kavita, Tin and Yannis as well as the partici-

pants of the Regenerative Medicine Summerschool, 2010 Athens for their articles and en-

thusiasm to work on this edition.

European greets,

Jeetindra Balak

Micky Las van Bennekom

S E E Y O U I N N E X T E D I T I O N ! Acknowledgement

Articles do not neces-

sarily reflect the opin-

ion of EMSA. All arti-

cles are the copyrights

of the EUROPEAN

MEDICAL STUDENTS‟

ASSOCIATION (EMSA).

We thank all of you for

your contributions.

The objectives of EMSA are:

° To form a network between European medical students to facilitate European integration and develop a sense of European

identity

° To represent and voice the opinions of the medical students of Europe

° To act as a forum for all medical students in Europe, to discuss topics related to the fields of medical education, medical ethics, and

medical research

° To promote the highest standards in European medical education and ensure the quality of healthcare in Europe

° To promote training, activities and projects related to health in Europe to the benefit of medical students and society

° To facilitate intercultural understanding by organizing social and cultural events

° To cooperate with other student organizations and with organizations representing the medical profession

A couple of the activities EMSA organises are: Teddy Bear Hospital, Twinning Project, Eurotalk, EMSA Summer Schools, EMS Council,

EMSA-skiing week, JEMSA and many more. For more information about EMSA projects you can contact the EMSA European Board

(mailto: eeb@emsa-europe.org) or visit our website at: www.emsa-europe.org.