SCIENCE FOUNDATION IRELAND:Stem cell technology has the potential to revolutionise the treatment of degenerative diseases and heal catastrophic injuries, and research at NUI is about to be translated into commercial therapies Regenerating tissue would mean avoiding the need for organ replacement and the associated problems with sourcing of donor organs.
THE RECENTLY announced Science Foundation Ireland funding of almost €10 million for the Regenerative Medicine Institute (Remedi) at NUI Galway could pave the way for clinical trials of new therapies and treatments for diseases such as cardiovascular disease, diabetes mellitus and osteoarthritis.
Remedi works at the cutting edge of research into stem cell biology and its translation into regenerative therapeutics. Amazing claims have been made for the potential of this exciting field but Remedi director Professor Tim O'Brien is cautious.
"I understand why patients go searching for new and possibly untried therapies," he says. "But we have to be careful. We are scientists and we have to make sure the therapies work and that they are safe. We ask the questions because we don't know the answers; if we knew the answers we wouldn't be asking them."
This is the second phase of the institute's work. "For the first five years we worked on establishing the programme, hiring people, building the infrastructure and starting basic research programmes in a number of areas," says Prof O'Brien.
This basic research was mainly in developing an understanding of fundamental stem cell biology and immunology - how the body's immune system responds to transplanted stem cells and genes. The group's work is exclusively concerned with adult stem cells, which are mainly found in bone marrow, blood, fat and muscle.
Stem cells have generated a great deal of interest because of their potential use in regenerative medicine and tissue engineering. They are undifferentiated or unspecialised cells - that is, cells that do not have a particular tissue type. Under certain conditions they differentiate into a particular cell type such as a bone cell, heart cell and so on.
"The fundamental characteristics of stem cells are the ability to grow and divide rapidly, and the ability to change, or differentiate, into cells that have very different characteristics from the original stem cell", explains Prof O'Brien.
"Our key research area is mesenchymal stem cells, often referred to as MSCs, which are found in bone marrow", he continues.
"They have the capacity to differentiate into connective tissue cells, including bone, fat, cartilage and muscle. Although these cells represent a very small fraction of the total cells in bone marrow, small numbers can be isolated from a tissue sample and grown to large numbers in the laboratory. They can then be induced to differentiate into different cell types under specific defined conditions. They also produce certain factors which promote healing. A stem cell is like a factory for these things."
And this is where the huge potential and some of the more fantastic claims for the science arises. Stem cells can be induced to build new tissue of various types including bone, cartilage and muscle. This is regenerative medicine, an evolving and exciting area of medical science. Regenerating tissue would mean avoiding the need for organ replacement and the associated problems with sourcing of donor organs. Developments in the field hold enormous potential for the treatment of currently untreatable degenerative diseases.
They have also given rise to hopes that stem cell therapy could be used to regenerate spinal cord tissue in order to cure catastrophic spinal injuries and treat degenerative brain conditions in a similar fashion. Such dramatic breakthroughs lie far in the future, however.
The basic research carried out in the first phase of the Remedi project will provide the foundation for the second phase, which aims to translate it into commercial products and technologies. "We had to understand the stem cell biology before we could work on the development of therapies", O'Brien points out. "For example, we had to understand why stem cells are abnormal when a patient is in a diseased state. Some of the problems associated with diabetes are related to dysfunctional cells. My own main clinical interest is in trying to grow new blood vessels in diabetic patients."
A central focus of Remedi has been on bringing the technologies of gene therapy and stem cell therapy together. For example, stem cells may be used to deliver genetic material to cells or genetic material can be delivered to stem cells to alter their behaviour and dictate what cells they can become or where they go in the body.
"Our vision is to develop a new and realisable paradigm for medicine in the future utilising minimally invasive therapeutic approaches to promote organ and tissue repair and regeneration", he continues. "Our goal is to undertake basic research in stem cell biology and to translate the outputs into new regenerative therapies.
"To achieve this, Remedi works with partners in hospitals which are members of the Irish Clinical Research Infrastructure Network, in Irish and overseas universities, and in industry, to translate and commercialise research outputs by developing regenerative medicine therapies for diseases such as diabetes mellitus and osteoarthritis."
The institute has now developed a critical mass of scientific research and industry partnerships with multinational and indigenous companies. It plans to bring new therapies and treatments for degenerative diseases like these to clinical trial.
"What we are trying to do is translate our research into new clinical treatments," says O'Brien. "To do this we have to go through a clinical trial process. We are currently finalising the pre-clinical process and hope to get regulatory approval to move to trials within the next year or two."
These treatments include "repairing" stem cells. "In some cases of diabetes there is a stem cell which is deficient in terms of producing a certain factor," O'Brien explains. "We can take those cells out, put the factor back in and put the cells back."
As Remedi's focus shifts towards translating research into human therapies, its partnerships with industry will take on a new significance. Advances in regenerative medicine will have important advantages for the progression of research and development in the medical device industry, which is critical to the economy of the west of Ireland.
The institute's already successful collaborative relationship with Medtronic, a global leader in medical device technologies, will continue to grow, while new partnerships have been established with indigenous companies including Creganna-Tactyx Medical, Procure, Ovagen, Proxy Biomedical, Ziel Biopharma and EnBIO.
There are also other commercial opportunities being explored by Remedi. "In parallel with the development of new therapies there is also the technology of cell manufacture and cell manipulation," O'Brien points out.
"You have to be able to isolate, grow, transplant and deliver them. For example, we are working with Medtronic to develop medical devices to deliver stem cells for patients requiring cardiovascular regeneration therapies. In terms of manufacture we can take 30 millilitres of stem cells from a donor and grow trillions of cells from them. There have to be safeguards put in place. How do you get a consistent product when you are dealing with complex living cells? We are working on all these areas, as well as others such as delivering the factors which aid healing made by the stem cells instead of using the stem cells themselves. There is a lot of spin-out potential from our stem cell biology research."
Looking to the future, Prof O'Brien is keen to play down some of the more overblown expectations which have grown up around stem cell research. "Stem cell technology does hold great potential for the development of new therapies", he says. "Like any other technology, stem cells will have a role to play and they will be used to treat some conditions for which we don't have good treatments at the moment - but the technology is not a magic bullet."
