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: [email protected]
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: [email protected]) or visit our website at: www.emsa-europe.org.
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