Gary Culliton looks at progress in the field of stem cell research and finds that Ireland could be a major player as developments unfold over the next five years, particularly in NUI Galway’s Regenerative Medicine InstituteIreland is set to be a significant player in the field of stem cell research over the next five years. A new clinical research facility is on the cards for Galway, which will provide beds for patients enrolled in stem cell therapy clinical trials.
“This country has a clinical network that will readily facilitate such trials,” said Prof Frank Barry, the Scientific Director of NUI Galway’s Regenerative Medicine Institute (REMEDI).
Stem cell research is at an interesting juncture, he said, where testing on humans is beginning to happen. “We have been making good progress in the recent past with animal studies,” said Prof Barry. “Over the next couple of years we’ll see the focus shifting toward clinical trials on humans.”
Stem cells (essentially repair cells) will have useful applications in areas such as joint disease, non-union fracture and, it is hoped, spine fusion. Orthopedics is set to be a strong target area for stem cell therapy, said Prof Barry.
Regenerative medicine is concerned with repairing, rather than replacing, tissue. In the future, stem cells or gene therapy, or a combination of the two, will mean a patient with an arthritic hip will have less damage to joints and more ability to use them.
Joint replacement surgery would thus be put off for a number of years – potentially an enormous medical, social and economic advance. REMEDI has international partners, who are interested in researching new therapies in the area of orthopedics.
The University of Aarhus in Denmark, for example, wants to carry out an arthritis clinical trial on patients at its campus, using stem cells generated in Galway. These early phase trials will be the first time such a study has been conducted in Europe. Aarhus will provide the clinical expertise and REMEDI will provide the stem cell expertise. There will be bigger studies conducted at a later stage.
Stem cells have no tissue-specific characteristics which would allow them to be identified as coming from for instance, the heart or the liver. They are found in early stage embryos, post-natal tissue such as the placenta and the umbilical cord, and they are found in adult tissues such as the bone marrow. REMEDI is concerned with the development of new protocols in stem cell therapy and gene therapy. REMEDI works with post-natal, rather than embryonic, stem cells.
These cells, depending on the signals they receive can change into many different tissue types. They can become heart cells or bone cells, for example, depending on the signals – usually biochemical – that they receive. That is where the therapeutic value comes from and the focus now is on cardiovascular, orthopedic and neuronal applications.
Stem cells grow well in the laboratory. In some cases a patient might be too sick to get stem cells from them. The bone marrow aspirate is uncomfortable — a large needle goes into the pelvis. But it is possible to work with either autologous (the patient’s own stem) cells or allogeneic cells (from a donor).
“We have devised a whole clinical critical path, to take us right through from the research we are doing now, to clinical trials in the future. Various elements are assembling to allow us, in the future, to do early phase clinical trials in Galway, involving the delivery of stem cells,” said Prof Barry.
The whole spectrum of work is scheduled to happen in Ireland, initially involving the in vitro tests, then animal studies and later human clinical trials.
REMEDI focuses in particular on bone marrow-derived stem cells. It is now engaged in developing methods to evaluate the therapeutic effectiveness of stem cells in animal models of targeted human diseases — cardiovascular, orthopedic and spinal cord.
Cardiac repair is being targeted, for example. Stem cells are delivered directly into the hearts of rats who have undergone myocardial infarction. The aim is to use stem cells to build up repair tissue, leading to some restoration of function.
Neurological applications, involving for instance the spinal cord, present more challenging targets but are potentially much more significant. Currently there is no effective treatment that can reverse spinal cord injury. The actor Christopher Reeve attracted world attention to this issue after he became a Paraplegic.
The Edinburgh-based company Stem Cell Sciences has a particularly strong expertise in neural stem cells. These are cells that are more fully programmed to differentiate into neuronal tissue.
Restoration of function
Prof Barry said REMEDI, which has been working in the area of the spinal cord for the last year, is testing this company’s stem cells on the Institute’s own spinal cord injury model in Galway. The aim is to see if those stem cells have any therapeutic effect and lead to any repair of damaged tissue or restoration of function (removal of paralysis).
Though testing is confined to animals, there is a great deal of interest in stem cell therapy for spinal cord injuries in humans. “Stem cells seem to have an effect but that needs to be confirmed in additional studies,” said Prof Barry.
Internationally, some clinics are treating people with spinal cord injury, using stem cells. Physician Carlos Lima and his team in Lisbon use stem cells taken from nasal tissue.
Various international reports indicate that stem cells seem to stimulate some reconnecting of severed or damaged tissue. Some of those neuronal junctions are being remade. There is evidence of a small reduction in paralysis.
Most of REMEDI’s funding comes from Science Foundation Ireland. The Institute has a €19 million budget for a five-year programme. One fifth of the budget comes from industry partners. There are two major partners — Metronic, a medical device company that has a facility in Galway, and Charles River Laboratories, a contract research animal testing organization that has premises in Mayo. Their contribution comes in the form of cash, technology, materials and expertise.
An active role
The partners play an active role in designing the research programmes. In return for their investment, they have some rights to the technology that comes out of the research.
The next phase of the Institute’s work will be more delivery-oriented. It will be about products and therapies coming out of the research. Plans are being drawn up for a second five -ear programme, REMEDI Two, to commence in 2009. The strategy in future is likely to include new spin off companies and licensing of stem cell technology to industry.