REMEDI
WELCOME NOTE FROM THE DIRECTOR
Regenerative Medicine
Institute
National Centre for
Biomedical Engineering
Science
National University
of Ireland Galway
T: 00 353 (0)91 49 5166
E: info@remedi.ie
W: www.remedi.ie
Prof. Timothy O' Brien,
Director of REMEDI
elcome to this issue of the REMEDI
newsletter which will highlight progress in
areas central to our goal of translating an
understanding of stem cell biology to regenerative
therapies.
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REMEDI continues to strengthen basic research in
stem cell biology with the appointment of Sanbing
Shen as Professor of Stem Cell Biology. Sanbing’s
research is described in this issue and we look
forward to welcoming him to REMEDI in
September 2011. Basic research at REMEDI will
be further strengthened as Uri Frank and Gerhard
Schlosser, with programmes in developmental
biology, have become REMEDI Principal
Investigators.
On the translational front REMEDI has increased
its focus on lung regeneration and the use of stem
cells in cancer therapy through collaborations with
John Laffey, Michael Kerin and Roisin O’Dwyer.
These collaborations have recently resulted in
publications in major international journals.
REMEDI continues to develop international
linkages which ensure that we play a central role in
the global development of regenerative medicine. I
recently visited the Wake Forest Institute of
REMEDI REVIEW
ISSUE 8
AUGUST 2011
IN THIS ISSUE
WELCOME NOTE FROM THE
DIRECTOR
REMEDI WELCOMES PROFESSOR
OF STEM CELL BIOLOGY
LEINSTER SCHOOL SCOOPS
DEBATING SCIENCE ISSUES
REMEDI SIGNS COLLABORATIVE
AGREEMENT WITH WFIRM
REMEDI TAKES PART IN EU
OSTEOARTHRITIS PROJECT
NEW STRUCTURED PHD
PROGRAMME IN BIOMEDICAL
ENGINEERING AND
REGENERATIVE MEDICINE
(BMERM)
IMAGING AND TREATMENT OF
BREAST CANCER
USING MESENCHYMAL STEM
CELLS
INTERVIEW WITH DR. AARON
LIEW
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Regenerative Medicine (WFIRM) in Winston
Salem, North Carolina to discuss collaborative
research projects. REMEDI has also developed a
partnership with Douglas Losordo at Northwestern
University, Chicago and Alan Stitt and Derek Brazil
at Queen’s University Belfast to study the biology
and therapeutic applications of endothelial
progenitor cells.
We are excited to participate in a number of
PRTLI5-funded structured graduate research
education programmes including one in Biomedical
Engineering and Regenerative Medicine led by
Peter McHugh at NUI Galway and highlighted in
this Newsletter.
I would like to especially
congratulate the 4 PhD students from REMEDI
who graduated recently.
While the global economic condition continues to
present challenges, our industry partners are all
actively involved in the research program at
REMEDI with many industry researchers working
alongside
REMEDI
staff
to
promote
commercialization of the research outputs. We will
continue to work closely with our industry partners
to ensure that any commercial opportunities arising
from our research are fully developed and exploited
and can provide an economic benefit to all.
REMEDI WELCOMES PROFESSOR
OF STEM CELL BIOLOGY
anbing Shen has been appointed as Professor of
Stem Cell Biology at NUI Galway. Prof Shen is
a world expert on animal models of genetic
diseases as well as artificial chromosome and
transgenesis.
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brain development at the School of Medical
Sciences. He also holds an Honorary Professorship
at the Tang Du Hospital in X’ian, China where he
works in close collaboration with the Neurosurgery
Department.
A graduate of Zhejiang University (formerly
Hangzhou) in China with a B.Sc in Genetics in
1983, Shen studied the developmental potential of
embryonic stem cells in mice, rabbits and pigs as
part of his M.Sc research at the Institute for
Developmental Biology, China Academy of Sciences
in Beijing. He was a recipient of the National
Science Fund Award for Distinguished Young
Scholars in 1986 for his pioneering work. He was
offered an ‘AIO’ scholarship by the Royal
Netherlands Academy of Arts & Sciences enabling
him to pursue a Ph.D at the Hubrecht Laboratory
in Utrecht. Under the supervision of Professors Dr
Siegfried de Laat, Paul van der Saag, Wiebe Kruijer
and Christine Mummery.
Shen has been working on translational medicine
combining stem cell technology with his rare
transgenic expertise, and generating a number of
genetic models for neurological diseases using loss
and gain of function approaches. He has had
considerable research success recently including the
generation of a number of genetic models tracking
a DISC1 gene shown to cause schizophrenia in a
Scottish family. Shen is currently validating novel
biomarkers and generating novel animal models for
neurodevelopmental
disorders
including
schizophrenia and autism.
Shen then moved to the lab of Nick Hastie at the
MRC Human Genetics Unit in Edinburgh where he
developed technology to amplify yeast artificial
chromosome. He was appointed a Lecturer at the
University of Aberdeen in 2002. He was promoted
to the position of Senior Lecturer in 2007 where he
formed a research team studying stem cells and
Stem cell technology provides tremendous
opportunities for transplantation medicine. iPS
(induced pluripotent stem cell) technology has been
developed in recent years to readily convert
patient’s somatic cells into pluripotent stem cells.
These cells can be made into different cell types to
treat patients with their own cells. This will
overcome the immuno-rejection problem which
commonly occurs in transplantation medicine.
2 REMEDI REVIEW
REMEDI WELCOMES PROFESSOR OF STEM CELL BIOLOGY
At REMEDI, Shen will lead a team to derive iPS cells from patients,
and to develop cell models for investigating mechanisms of the
diseases and for drug screening towards the development of novel
pharmacological treatments. He also plans to develop an artificial
chromosome technology to correct the genetic defectiveness in
patients’ iPS cells before cell transplantation.
part of our effort will be to ensure that our translational targets are
linked to research in basic science. Sanbing’s appointment will link
our basic and translational research programmes at REMEDI.”
Professor Tim O’Brien, Director of REMEDI, states that Sanbing’s
appointment to the Chair of Stem Cell Biology at NUI Galway will
strengthen research in fundamental stem cell biology and so underpin
translational efforts in regenerative medicine. “A fundamental
understanding of basic stem cell biology will be essential to the future
translation of regenerative medicine therapies to the clinic. A major
LEINSTER SCHOOL SCOOPS DEBATING SCIENCE ISSUES
t. Vincent’s Secondary School, Dundalk, Co. Louth were
declared the All-Ireland winners of Debating Science Issues (DSI)
2011. The grand final which took place at the Science Gallery
at Trinity College Dublin on April 14 was the result of a field of 56
schools narrowing to just four. The team from Dundalk successfully
persuaded Professor Tom Sherry, Dean of Science at National
University of Ireland Galway, Dr. Amy Sanders, Wellcome Trust
Special Projects Manager, and Professor Orla Sheils Lecturer in
Pathology and Medical Jurisprudence at Trinity College, that
“animal testing is necessary for the advancement of disease
treatment”. Coláiste an Phiarsaigh of Glanmire, Co. Cork were the
Runners up at the Final. Ulster was represented by St. Catherine’s
Vocational School, Killybegs, Co. Donegal and Connacht by St.
Joseph’s College Garbally, Co. Galway.
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biomedical, bioethical workshop to facilitate discussion on the ethical
issues raised by stem cell research, genetically modified food,
nanotechnology, health and self-testing kits or flu vaccinations.
School students research further in preparation for the debate motion
related to the initial workshop. From there, the debate motions
circulate so that students debate on an array of controversial topical
issues.
Boston Scientific and NUI
Galway’s College of Science sponsored
the provincial trophies and prizes.
Debating Science Issues is a cross border schools science debating
competition supported by a Wellcome Trust People Award for four
consecutive years and involves eight collaborating partners: the
Regenerative Medicine Institute (REMEDI) at NUI Galway, W5 in
Belfast, Biomedical Diagnostics Institute (BDI) at DCU, Royal
College of Surgeons Ireland, CRANN at TCD, CLARITY at UCD,
Tyndall National Institute and Alimentary Pharmabiotic Centre both
at UCC. Co-ordinated by REMEDI’s Outreach Officer Danielle
Nicholson, the competition encourages young people to engage in
debate on the cultural, societal and ethical implications of advances
in biomedical science. Schools taking part initially receive a 3 hour
REMEDI SIGNS COLLABORATIVE AGREEMENT WITH WFIRM
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he Regenerative Medicine Institute (REMEDI) along with the
Network of Excellence for Functional Biomaterials (NFB) also
based at NUI Galway formally signed a Memorandum of
Understanding with Wake Forest Institute for Regenerative Medicine
(WFIRM) recently. WFIRM is one of the leading institutes in tissue
engineering and regenerative medicine in the USA.
Professor Timothy O’Brien, Director of REMEDI at NUI Galway,
said: “I look forward to the potential that this agreement offers to
both REMEDI and WFIRM to accelerate the translation of
regenerative medicine from basic research to the clinic”.
Speaking at the signing, Professor Abhay Pandit, Director of the NFB,
NUI Galway, said: “This agreement facilitates the establishment of
student and faculty exchanges, research collaborations and the codevelopment of any specific tissue engineering and regenerative
medicine-related projects which may have academic, clinical and
commercial implications”.
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The Wake Forest Institute for Regenerative Medicine is part of Wake
Forest University Baptist Medical Center in Winston-Salem, North
Carolina. The centre has built up a significant reputation in the
development of tissue engineering and regenerative medicine and is
renowned for development from concept to translation in the clinic.
3 REMEDI REVIEW
REMEDI TAKES PART IN EU OSTEOARTHRITIS PROJECT
rthritis is affecting increasing numbers of people in Ireland, with
an estimated three-quarters of a million men and up to 1 in 6
women affected. The vast majority of people with arthritis suffer
from osteoarthritis, the most common form of degenerative arthritis.
REMEDI researchers began an FP7 EU-funded project called
GAMBA (Gene Activated Matrices for Bone and Cartilage
Regeneration in Arthritis) in late 2010, which ultimately aims to use
regenerative medicine therapies to find new methods of treatment for
arthritis through the use of stem cells, gene therapy and materials to
stimulate self-healing.
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REMEDI’s orthobiologics group led by Dr. Mary Murphy is working
in collaboration with a number of partners from Germany, France,
Italy, the Netherlands and Switzerland. GAMBA is coordinated by
the University Hospital Rechts de Iser at the Munich Technical
University, Germany. REMEDI will receive €400,000 in funding
over the three years of the project.
REMEDI researchers, Dr. Eric Farrell and Niamh Fahy along with
the gene therapy research group led by Dr. Thomas Ritter aim to
develop methods for immune-modulation in the osteoarthritic joint
to prevent progression of osteoarthritis and pain. Pro-inflammatory
factors normally produced in the diseased joint will be harnessed as
triggers for initiation of an anti-inflammatory response. This will be
achieved by the use of gene therapy with the production of an antiinflammatory molecule called interleukin-10 which is controlled by
a switch that is turned on as the joint becomes inflamed. Other
strategies for temporal repair in osteoarthritis will focus on damaged
cartilage and bone.
REMEDI, along with the other partners in the project, also aims to
develop greater awareness and debate on the societal and ethical
issues that affect patients and the public alike. GAMBA will develop
and use outreach methods called patient and citizen panels in order
to increase awareness of the role that regenerative is playing in
finding new therapies to treat osteoarthritis. Already an outreach
project between patients and researchers has been rolled out in
GAMBA’s dissemination point in Munich. Galway will host a future
event to help improve general awareness of nano-medicine among
the general public here.
Dr. Mary Murphy, who is leading the GAMBA project at REMEDI,
says that “GAMBA aims to bring the power of nanomedicine to the
treatment of osteoarthritis by focusing on development of techniques
to promote self-healing of the cells affected by the disease. Advances
in this area will ultimately lead to novel therapies and, most
importantly, an improved quality of life for people with arthritis.”
NEW STRUCTURED PHD PROGRAMME IN BIOMEDICAL
ENGINEERING AND REGENERATIVE MEDICINE (BMERM)
he medical technology industry is critically important
internationally and is one of the pillars of the Irish economy, with
a tremendous potential for growth. It is dependent on having a
highly educated and trained workforce and a strong research and
innovation capability. Biomedical engineering and regenerative
medicine are at the heart of this growth potential and this structured
PhD programme is designed to produce graduates who will be the
next generation of leaders in the industry and in academic research
and education in the field.
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This four year structured PhD Programme in
Biomedical Engineering and Regenerative
Medicine will be delivered by a core
partnership of institutions: National
University of Ireland Galway (Coordinator),
University of Limerick and University College
Cork and will be linked with a wider
consortium of partner institutions nationally
and internationally, including: Galway-Mayo
Institute of Technology, Institute of
Technology Sligo, University of Ulster,
Queen’s University Belfast, Georgia Institute
of Technology, USA, University of Pittsburgh,
USA, Duke University, USA, Rice University, USA, Mayo Clinic,
USA, RWTH Aachen University, Germany, Georgia Tech Ireland, and
the Irish Medical Devices Association (IMDA).
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BMERM combines a PhD research project with a unique didactic
and experiential learning programme, resulting in an unparalleled
learning experience for the student in terms of its combination of
world-class research and focused clinical and industrial engagement,
the latter facilitated by the direct involvement of IMDA with is
membership of over 100 medical technology companies in Ireland.
At the core of the programme is the PhD research project, performed
in collaboration with internationally renowned investigators, in one
of the following five areas: Functional Biomaterials; Mechanics of
Biological Cells, Tissues and Systems; Bioelectronics and
Rehabilitation Engineering; Regenerative Orthobiologics and
Neurotherapeutics; Regenerative Cardiovascular Therapeutics. The
BMERM didactic and experiential learning programme involves the
following elements: Student Placement, Annual Summer School,
Medical Sciences and Clinical Attachment module, unique
“BioInnovate” modules for medical technology innovation, design
and entrepreneurship training, Generic Skills modules, and a range of
advanced discipline-specific modules aligned with the five research
areas.
Professor Noel Caplice, REMEDI and Professor of Cardiovascular
Science/Consultant Cardiologist, CUH/UCC said, “This is an exciting
interaction between universities that are already co-operating on stem
cell and cardiovascular thematic research. We believe this BMERM
interaction will only strengthen this collaboration.
6 REMEDI REVIEW
IMAGING AND TREATMENT OF BREAST CANCER
USING MESENCHYMAL STEM CELLS
esenchymal stem cells (MSCs) are adult stem cells that appear
to have the ability to “find” tumours. Tumours release signals
that stimulate MSCs to migrate towards them and become
incorporated into the tumour. Researchers at REMEDI along with
some leading international partners have recently published research
reporting the ability to track MSCs in real time as they migrate to
the tumour site, followed by therapy to reduce tumour growth.
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the MSCs were engrafted in their intended destination, a therapeutic
dose of radioactive iodide was administered. The ability to image
the MSCs to confirm engraftment in tumour tissue allowed
researchers to deliver therapy mediated by the MSCs at the optimal
timepoint, sparing surrounding healthy tissues. This resulted in a
significant reduction in tumour growth, with no negative side effects
observed.
As a result of this efficient “homing” to the tumour site, many studies
have been performed attempting to use MSCs for delivery of
therapeutic agents directly to tumour tissue, while sparing healthy
surrounding tissue. One of the major challenges to this approach is
the possibility of the MSCs residing in other organs in the body rather
than their intended destination of the tumour tissue.
The results of the work were recently published in the highly rated
international journal “Stem Cells” by Dr. Róisín Dwyer and Prof.
Michael Kerin, in collaboration with research groups at REMEDI
led by Prof. Frank Barry, Dr. Mary Murphy and Prof. Timothy
O’Brien. Colleagues from the Schools of Medicine and Physics in
NUI Galway also contributed significantly.
In work carried out at NUI Galway, MSCs were engineered to take
up a radioactive tracer, which could then be tracked as the cells
travelled towards the breast tumour. Imaging was performed using
a BazookaSPECT imaging system designed by researchers at the
Center for Gamma Ray Imaging at the University of Arizona in
Tucson. The imaging system tracks the MSCs in real time to
determine the time point at which they reached the tumour site. Once
The results of the breast cancer study are extremely promising, as
MSCs can target many different tumour types so this approach has
potential applications in a range of other cancers. This work received
financial support from Science Foundation Ireland, the Health
Research Board, Cancer Research Ireland, and also the University of
Arizona Center for Gamma Ray Imaging which is funded in part by
the US National Institute of Health (NIH).
INTERVIEW WITH DR. AARON LIEW
r. Aaron Liew is a postdoctoral researcher at REMEDI. In a
recent interview he described the focus of his research at
REMEDI as well as his interest in regenerative medicine.
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Aaron came from Malaysia in 1995. He completed his undergraduate
medical degree in the Royal College of Surgeons in Ireland (RCSI) in
2000. He completed the Higher Specialist Training (HST) in two
specialties; Diabetes & Endocrinology and General Internal Medicine
in June 2010 before joining REMEDI as a postdoctoral research
fellow. In between his HST, he spent three years full time in REMEDI,
prior to obtaining his PhD degree in 2008. His PhD theses focused on
the effect of diabetes related dysfunction of endothelial progenitor
and mature endothelial cells.
Aaron is currently involved in the Cell Therapy and Angiogenesis for
Peripheral Vascular Disease work programme under the supervision
of Professor Timothy O’Brien. This project is jointly funded by
Science Foundation Ireland (SFI) and industry partner Medtronic
Vascular. His current research focuses on the efficacy of mesenchymal
stem cells (MSCs) and Ephrin B2-expressing MSC therapy in a model
of hindlimb ischemia. He is also interested in the role of endothelial
progenitor cells (EPCs) especially in the diabetic setting, and nonviral gene therapy approaches such as electroporation for improving
MSC function.
“Currently, there is a paradigm shift of research focus into
translational research involving multidisciplinary collaboration
whereby findings in basic science research are translated into medical
practice with meaningful health outcomes. Regenerative medicine
which falls under this remit holds the promise of regenerating
damaged tissues and organs in the body by stimulating previously
irreparable tissues to repair themselves. I am interested in the
potential therapeutic role of stem cell, in particular, the MSC in
critical limb ischaemia (CLI). CLI, which is a condition characterised
by the presence of rest pain or impending tissue loss secondary to an
objectively proven arterial occlusive disease, is predominantly caused
by atherosclerosis. The increase in the prevalence of diabetes and an
aging population resulted in the increase in this condition. To date,
the only option available for patients with CLI
who are not amenable for either surgical or
endovascular revascularisation, is amputation.
Therefore, novel treatments such as MSC-based
therapy are urgently needed”, Aaron says.
“There are multiple data from pre-clinical
studies and early human trials which
demonstrate that MSC-based therapy in
patients with CLI are safe with some suggestion of clinical efficacy.
Further larger phase 3 clinical trials are required to determine the
efficacy of MSC-based therapy in patients with CLI. The close
proximity of the National GMP Facility in REMEDI, the Clinical
Research Facility Galway (CRFG) and the Galway University
Hospital (GUH) renders Galway the most ideal site in Ireland to
conduct a successful stem cell-based clinical trial. Furthermore, there
are also vast opportunities to collaborate with many researchers
within the university”, he added.
Aaron in collaboration with Professor Lluis Mir and Dr. Franck
Andre from Vectorology and Anti-cancerous Therapeutics, Institute
Gustave-Roussy, Villejuif, France, has successfully secured a Ulysses
Grant from the Irish Research Council for Science, Engineering and
Technology (IRCSET) in partnership with Teagasc, the French
Embassy, the French Foreign Ministry, and Égide. The Ulysses
programme facilitates the exchange of innovative ideas and
approaches between Irish and French researchers and the
development of mutual research projects by supporting young Irish
researchers visiting France and reciprocal visits by young French
researchers to Ireland of which the main purpose is to establish future
research networks. Aaron’s research project will determine the
optimal method for electrotransfection of human MSCs for clinical
use. Cliniporator, which is a state-of-the-art electroporator and is
currently utilised in the clinical settings in France will be used in this
project. “This Ulysses grant not only allows us to determine the best
approach to genetically modify the MSC to enhance its therapeutic
effect, but, it also facilitates future research collaboration with
Professor Mir and Dr. Andre’s team in France”, Aaron concluded.