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WELCOME NOTE FROM THE DIRECTORWelcome 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
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 next-generation 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 co-sponsored 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.
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,
REMEDI TO WORK WITH CHINESE UNIVERSITIES
REMEDI REVIEW
Prof. Timothy O’BrienDirector of REMEDI,Head of Medicine at NUI Galway
REMEDI REVIEWISSUE 9SEPTEMBER 2012
Regenerative Medicine Institute
National Centre for Biomedical Engineering Science
National University of Ireland, Galway
T: +353 91 495166
W: www.remedi.ie
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
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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.”
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 semi-finals, 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.
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.
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
BIOINNOVATE SUCCESS
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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programmes to deliver a ‘best in class’ graduate and further demonstrates NUI Galway’s leadership position in the medical technology area.”
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.
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).
L to R: Ana Cimpian, Paul Lohan, Sean Gaynard and Fiona Griffin
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).
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 self-renew (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 cellsNo treatments using MSCs are yet available. However, several possibilities for their use in the clinic are currently being explored.
Bone and CartilageThe 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.
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 repairSome 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 diseasesSeveral 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 futureMany 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/mesenchymal-stem-cells-other-bone-marrow-stem-cells
AN INTRODUCTION TO MESENCHYMAL STEM CELLS (MSCS)
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STEM CELLS AND RADIATIONBone 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 t r e a t m e n t s t r a t e g i e s to help avoid their p o t e n t i a l l y 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 BEATHeart 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.
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-nanotube-based 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.
Dr. Valerie Barron
