REMEDI REVIEW
WELCOME NOTE FROM THE DIRECTOR
Regenerative Medicine
Institute
National Centre for
Biomedical Engineering
Science
National University of
Ireland, Galway
T: +353 91 495166
E: info@remedi.ie
W: www.remedi.ie
Welcome to this edition of the REMEDI
Newsletter. The past year has been a particularly
eventful time for us and a number of our recent
successes are highlighted in these pages.
Earlier this year, during an Irish Government trade
visit to China, REMEDI formally commenced
collaborations with Institutes at two prestigious
Chinese Universities, the Shanghai Jiao Tong
University and the Fourth Military Medical
University. Professor of Stem Cell Biology Sanbing
Shen signed the collaborative agreement on behalf
of REMEDI in a reception that was attended by An
Taoiseach Enda Kenny. REMEDI will work closely
with both Institutes in the area of regenerative
medicine clinical trials.
We were privileged to take part in the Volvo
Ocean Race final stopover in Galway in June
which was a wonderful opportunity to exhibit
some stem cell learning tools developed through
the EuroStemCell project. An unprecedented
number of people got to interact with the exhibit
Prof. Timothy O’Brien
Director of REMEDI,
Head of Medicine at NUI
Galway
REMEDI REVIEW
ISSUE 9
SEPTEMBER 2012
IN THIS ISSUE
WELCOME NOTE FROM
THE DIRECTOR
REMEDI TO WORK WITH
CHINESE UNIVERSITIES
BIOINNOVATE SUCCESS
STELLA SAILS IN THE
VOLVO OCEAN RACE
AN INTRODUCTION TO
MESENCHYMAL STEM
CELLS (MSCS)
STEM CELLS AND
RADIATION
NANOMATERIALS IN A
HEART BEAT
WWW.REMEDI.IE
and learn about stem cells including President of
Ireland, Michael D Higgins and An Taoiseach Enda
Kenny.
Our publication outputs continue to grow. In
the last number of months REMEDI researchers
have published work in prestigious international
journals such as Nature Immunology, Blood and
Biomaterials, illustrating the quality and breadth of
research being undertaken at REMEDI.
Our researchers are focussed on developing nextgeneration solutions in the regenerative medicine
field and we are continuing to work closely with
our industry partners to achieve this aim. For
example have recently commenced a new project
in the area of bone regeneration with DuPuy cosponsored by the Irish Research Council. We
firmly believe this aim can best be achieved by
closer cooperation between academic centres and
industry which will ensure that when commercial
opportunities arise they are efficiently developed
to the mutual benefit of all.
REMEDI TO WORK WITH CHINESE
UNIVERSITIES
In March 2012 REMEDI signed collaborative
agreements with the Shanghai Institute
for Paediatric Research and the Tangdu
Neurosurgery & Neurology Hospital. These
two research institutes are based in two
leading Chinese Universities, Shanghai Jiao
Tong University (SJTU) and the Fourth Military
Medical University (FMMU), Xi’an. The FMMU
is one of the top three medical schools in China
and has pioneered neurosurgery and transplant
procedures in China.
The agreement was signed during a Trade and
Investment Mission to China by An Taoiseach
Enda Kenny and Minister Richard Bruton TD.
Also at the signing were NUI Galway President,
Dr Jim Browne (front row, right) and Professor
of Stem Cell Biology Sanbing Shen on behalf of
REMEDI. (back now, second from right)
The agreement will see REMEDI work closely
with both Chinese partners in a number of
research areas and will facilitate student and
researcher exchange between Galway and
China.
One of the first joint research projects will
involve Professor Shen, who is developing
cutting edge induced pluripotent stem cell (iPS)
technology at REMEDI. iPS technology involves
generating “embryonic-like” stem cells from
adult cells and has been hailed as one of the top
scientific breakthroughs in the last number of
years. Professor Shen and Professor Frank Barry
at REMEDI are the first scientists to successfully
generate iPS cells from human biopsies in Ireland.
REMEDI will also work with both Chinese
institutes to develop joint clinical trial
programmes in the area of regenerative medicine.
Professor Timothy O’Brien, Director of REMEDI
at NUI Galway: “REMEDI’s commitment to
clinical trials of treatment using adult stem cells
will be greatly enhanced by these collaborations
as both institutions have similar scientific and
clinical interests as NUI Galway. This will provide
for much more extensive patient involvement in
clinical trials, as well as the sharing of expertise
in the design of the trials and the analysis of the
resulting data.”
Speaking at the singing of the agreement in
Shanghai and Beijing, President of NUI Galway,
Dr Jim Browne said: “NUI Galway has a range of excellent
relationships with Chinese higher education institutions in
areas from marine science to engineering to human rights.
These new agreements in the area of regenerative medicine
with our Chinese partners will bring new and positive
developments to our activities in the biosciences. These
partnerships will see NUI Galway and these two significant
Chinese universities develop joint research programmes
which will encourage the exchange of faculty, researchers, and
graduate students with the objective of fostering academic
cooperation and collaboration between both parties.”
BIOINNOVATE SUCCESS
Two REMEDI PhD students Paul Lohan and Sean Gaynard along
with two other PhD students from NUI Galway, Ana Cimpian,
and Fiona Griffin, reached the final of the Ireland Fund Business
Plan competition held at the Aviva Stadium in Dublin on Tuesday,
19 June, 2012. Their innovative medical device business idea
secured the team joint third place in the competition which seeks
out the best business ideas from nine Universities across Ireland.
For the competition, 19 teams were shortlisted for the semifinals, from a large pool of applicants, from which four teams
were selected for the final based on their business plan sales
pitch to the judging panel.
L to R: Ana Cimpian, Paul Lohan, Sean Gaynard and Fiona Griffin
programmes to deliver a ‘best in class’ graduate and further
demonstrates NUI Galway’s leadership position in the medical
technology area.”
The team of four are first-year PhD students in the Structured
PhD Programme in Biomedical Engineering and Regenerative
Medicine (BMERM) and the project was created as part of their
participation in the BioInnovate Ireland programme. BioInnovate
Ireland is a specialist training and collaboration programme in
medical device innovation modelled on Stanford University’s
prestigious Biodesign Programme.
Dr Mark Bruzzi, BioInnovate Ireland Programme Director added
that the interaction between the postgraduate multi-disciplinary
teams and the BioInnovate Ireland Fellows, Academics, Clinicians
and Industry Experts has produced a class of students who will
have a significant long-term impact on the graduate medical
technology market place in Ireland.
Professor Peter McHugh, Director of BMERM at NUI Galway,
commented: “This is a fantastic achievement for the students,
the BioInnovate and BMERM programmes and the University.
It really shows the synergy that can be achieved between
BMERM is an inter-disciplinary and inter-institutional structured
PhD programme, led by NUI Galway, that is funded under
the Programme for Research in Third-Level Institutions
(PRTLI) Cycle 5 and co-funded under the European Regional
Development Fund (ERDF).
STELLA SAILS IN THE VOLVO OCEAN RACE
REMEDI and EuroStemCell exhibited the Stem Cells for
Blood Transfusions public engagement tool at the NUI
Galway Exploration Pavilion during the Volvo Ocean Race
final stopover in Galway port. The Volvo Ocean Race is a
round the world yacht race, held every three years and for a
week from June 30th to July 6th 2012, hundreds of thousands
of international visitors had the opportunity to interact with
a stem cell marble game and Stella, a ‘patient’ in need of
regenerative medicine treatments. Amongst the many illustrious visitors who learned about stem
cells from Stella were Minister for Communications, Energy
and Natural Resources Pat Rabbitte, President of Ireland
Michael D. Higgins and An Taoiseach Enda Kenny.
Danielle Nicholson the REMEDI Outreach Officer remarked,
“The exhibit is brilliant! It attracts the attention of people
of all ages and backgrounds. Its clever design activates users
to ask questions and learn about stem cells in a visual, tactile
manner. Actually, the week-long event offered a fantastic
opportunity to discuss the research ongoing at REMEDI, to
promote the work and tools of EuroStemCell and to debunk
many of the misconceptions that people have heard about
and read.”
The public engagement kit which also includes a kiosk with
quiz questions was developed by EuroStemCell partners the
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REMEDI PhD student Niamh Fahy explains stem cell concepts to
NUIG President James Browne and An Taoiseach Enda Kenny
MRC Centre for Regenerative Medicine at the University of
Edinburgh, together with scientists at Glasgow University and
the Irish and Scottish National Blood Transfusion.
EuroStemCell is a partnership of scientists, clinicians, ethicists,
social scientists and science communicators to help European
citizens make sense of stem cells research. EuroStemCell is
funded by the European Commission’s Seventh Framework
Programme (FP7).
AN INTRODUCTION TO
MESENCHYMAL STEM
CELLS (MSCS)
What can mesenchymal stem cells do?
MSCs are an example of tissue or ‘adult’ stem cells. They are
‘multipotent’, meaning they can produce more than one type
of specialized cell of the body, but not all types. MSCs make
the different specialized cells found in the skeletal tissues. For
example, they can differentiate - or change - into cartilage
cells (chondrocytes), bone cells (osteoblasts) or fat cells
(adipocytes).
Scientists at REMEDI are investigating how MSCs might be
used to treat bone and cartilage diseases. Some MSC research
is also exploring therapies for other diseases such as vascular
disease.
Some early research suggested that MSCs might also
differentiate into many different types of cells that do not
belong to the skeletal tissues, such as nerve cells, heart
muscle cells, liver cells and endothelial cells, which form the
inner layer of blood vessels. These results have not been
confirmed to date. In some cases, it appears that the MSCs
fused together with existing specialized cells, leading to false
conclusions about the ability of MSCs to produce certain
cell types. In other cases, the results were an artificial effect
caused by chemicals used to grow the cells in the lab.
Where are mesenchymal stem cells found?
MSCs were originally found in the bone marrow. There have
since been many claims that they also exist in a wide variety
of other tissues, such as umbilical cord blood, adipose (fat)
tissue and muscle. It has not yet been established whether the
cells taken from these other tissues are really the same as, or
similar to, the MSCs of the bone marrow.
The bone marrow also contains many different types of cells.
Among them are blood stem cells (also called hematopoietic
stem cells; HSCs) and a variety of different types of cells
belonging to a group called ‘mesenchymal’ cells. MSCs make
up about 0.001-0.01% of all the cells in your bone marrow.
It is fairly easy to obtain a mixture of different mesenchymal
cell types from adult bone marrow for research. But isolating
the tiny fraction of cells that are mesenchymal stem cells is
more complicated. Some of the cells in the mixture may be
able to form bone or fat tissues, for example, but still do
not have all the properties of mesenchymal stem cells. The
challenge is to identify and pick out the cells that can both selfrenew (produce more of themselves) and can differentiate
into three cell types – bone, cartilage and fat. Scientists have
not yet reached a consensus about the best way to do this.
Developing new treatments using mesenchymal
stem cells
No treatments using MSCs are yet available. However,
several possibilities for their use in the clinic are currently
being explored.
Bone and Cartilage
The ability of MSCs to differentiate into bone cells called
osteoblasts has led to their use in early clinical trials
investigating the safety of potential bone repair methods.
These studies are looking at possible treatments for localized
skeletal defects (damage at a particular place in the bone).
Other research is focussed on using MSCs to repair cartilage.
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Cartilage covers the ends of bones and allows one bone to
slide over another at the joints. It can be damaged by a sudden
injury like a fall, or over a long period by a condition like
osteoarthritis, a very painful disease of the joints. Cartilage
does not repair itself well after damage. The best treatment
available for severe cartilage damage is surgery to replace
the damaged joint with an artificial one. Because MSCs can
differentiate into cartilage cells called chondrocytes, scientists
hope MSCs could be injected into patients to repair and
maintain the cartilage in their joints. Researchers are also
investigating the possibility that transplanted MSCs may
release substances that will tell the patient’s own cells to
repair the damage.
Heart and blood vessel repair
Some studies in mice suggest that MSCs can promote formation
of new blood vessels in a process called neovascularisation.
MSCs do not make new blood vessel cells themselves, but
they may help with neovascularisation in a number of ways.
For example, they may release proteins that stimulate the
growth of other cells called endothelial precursors – cells that
will develop to form the inner layer of blood vessels. Such
studies on animals have led researchers to hope that MSCs
may provide a way to repair the blood vessel damage linked
to heart attacks or diseases such as critical limb ischaemia.
A number of early stage clinical trials using MSCs in patients
are currently underway but it is not yet clear whether the
treatments will be effective.
Inflammatory and autoimmune diseases
Several claims have been made that MSCs are able to avoid
detection by the immune system and can be transplanted
from one patient to another without risk of immune rejection
by the body. However, these claims have not been confirmed
by other studies. It has also been suggested that MSCs may
be able to slow down the multiplication of immune cells in
the body to reduce inflammation and help treat transplant
rejection or autoimmune diseases. Again, this has yet to
be proven and much more evidence is needed to establish
whether MSCs could really be used for this kind of application.
Current research and the future
Many hurdles remain before this kind of treatment can become
a reality. For example, when MSCs are transplanted, most of
them are rapidly removed from the body. Researchers are
working on new techniques for transplanting the cells, such
as developing three-dimensional structures or scaffolds that
mimic the conditions in the part of the body where the cells
are needed. These scaffolds will hold the cells and encourage
them to differentiate into the desired cell type.
Research into therapies using MSCs is still in its infancy. A great
deal more work is needed before such therapies can be used
routinely in patients. Questions remain about how the cells
can be controlled, how they will behave when transplanted
into the body, how they can be delivered to the right place so
that they work effectively and so forth. By studying how these
cells work and interact within the body, researchers hope to
develop safe and effective new treatments in the future.
This fact sheet was created by REMEDI PhD students Mikey
Creane and Clara Sanz Nogues. For the full fact sheet on MSCs
go to: http://www.eurostemcell.org/factsheet/mesenchymalstem-cells-other-bone-marrow-stem-cells
STEM CELLS AND RADIATION
Bone marrow transplantation is a treatment for blood cell
diseases such as bone marrow failure following nuclear
accidents, leukaemia and some auto-immune diseases where
the body’s immune system attacks the host.
To allow transplanted bone marrow stem cells (HSC) from
a donor to engraft and survive in the recipient, the patient’s
own HSC have to be first removed by irradiation and/or
chemotherapy treatment. However some other important
stem cells such as mesenchymal stem cells (MSC) that are
required to support blood cell formation can actually survive
irradiation, and until now how they do this was unknown. In an
upcoming paper accepted in the journal Stem Cells, REMEDI
scientists describe how MSC can survive irradiation and are
even able to repair irradiation-induced damage to their DNA.
This research also has implications in the treatment of certain
cancers. Some cancer stem cells, such as breast cancer
stem cells are known to survive irradiation and as a result
if the cancer returns post-irradiation, it is frequently more
aggressive. MSCs can also promote angiogenesis, or the
formation of blood vessels which in turn can support tumour
growth and these cells have also been shown to switch off the
immune response to the tumour. By understanding how these
stem cells survive irradiation, scientists will be better able to
develop new
treatment
strategies
to
help
avoid
their
potentially
h a r m f u l
influence.
Tara Sugrue the PhD student who carried out this work in
collaboration with Professor Noel Lowndes at the Centre for
Chromosome Biology at NUI Galway, has recently received
a short-term fellowship from the European Molecular Biology
Organization (EMBO) to continue this work at the University
of Basel in Switzerland. EMBO is a grouping of leading life
scientists that fosters and supports new generations of
researchers. EMBO short-term fellowships fund research
visits of up to three months to laboratories in Europe and
elsewhere in the world. The aim is to facilitate valuable
collaborations with research groups applying techniques
unavailable in their own laboratories.
Tara also recently won Best Student Poster prize at the Royal
Academy of Medicine Biomedical Science Conference in
Galway.
NANOMATERIALS IN A HEART BEAT
Heart disease is the leading cause of death in Ireland. Once
damaged by heart attack, cardiac muscle has very little capacity
for self-repair and at present there are no clinical treatments
available to repair damaged cardiac muscle tissue.
Over the last 10 years, there has been tremendous interest
in developing a cell-based therapy to address this problem.
Since the use of a patient’s own heart cells is not a viable
clinical option, many researchers are working to try to find
an alternative source of cells that could be used for cardiac
tissue repair.
REMEDI researchers Dr Valerie Barron and Dr Mary Murphy
have brought together a multi-disciplinary team of Irish
materials scientists, physicists and biologists from REMEDI
and Trinity College Dublin to address this problem.
The researchers recognised that carbon nanotubes, a widely
used nanoparticle, is reactive to electrical stimulation. They
then used these nanomaterials to create cells with the
characteristics of cardiac progenitors, a special type of cell
found in the heart, from adult stem cells.
“The electrical properties of the nanomaterial triggered a
response in the mesenchymal (adult) stem cells, which we
sourced from human bone marrow. In effect, they became
electrified, which made them morph into more cardiac-like
cells”, explains REMEDI’s Valerie Barron. “This is a totally
new approach and provides a ready-source of tailored cells,
which have the potential to be used as a new clinical therapy.
Excitingly, this symbiotic strategy lays the foundation stone for
other electroactive tissue
repair applications, and
can be readily exploited
for
other
clinically
challenging areas such as
in the brain and the spinal
cord.”
This work has recently
been
published
in
two leading scientific
journals,
Biomaterials
and
Macromolecular
Bioscience, and was carried
out in collaboration with
Werner Blau from Trinity
College Dublin.
Dr. Valerie Barron
The electrical stimulation of carbon nanotubes to provide a
cardiomimetic cue to MSCs.
Mooney E, Mackle JN, Blond DJ, O’Cearbhaill E, Shaw G, Blau
WJ, Barry FP, Barron V, Murphy JM.
Biomaterials. 2012 Sep;33(26):6132-9. Epub 2012 Jun 6.
In vitro characterization of an electroactive carbon-nanotubebased nanofiber scaffold for tissue engineering.
Mackle JN, Blond DJ, Mooney E, McDonnell C, Blau WJ, Shaw
G, Barry FP, Murphy JM, Barron V.
Macromol Biosci. 2011 Sep 9;11(9):1272-82. doi: 10.1002/
mabi.201100029. Epub 2011 Jul 4.