2004 IRISH SCIENTIST YEAR BOOK

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National University of Ireland, Galway
Frank Barry
Regenerative Medicine Institute


Micrographs of undifferentiated human mesenchymal stem cells grown in monolayer culture (A) and after differentiation along the bone (B), fat (C) and cartilage pathways (D) and (E)

The Regenerative Medicine Institute (REMEDI) at NUI, Galway, was established in 2004 through a Science Foundation Ireland Centre for Science Engineering and Technology (CSET) award and industry funding totalling �19m. Researchers at REMEDI conduct basic and applied research in regenerative medicine, which is an emerging field that approaches the repair or replacement of tissues and organs by incorporating the use of cells and genes to regenerate healthy tissues. REMEDI is located in the National Centre for Biomedical Engineering Science (NCBES), which includes the National Gene Vector Laboratory, a clinical grade cell and vector production facility. The goal of REMEDI is to explore the synergies of gene therapy and adult stem cell therapy to promote tissue repair and regeneration, and bring these therapies to clinical application.

Adult human stem cells have been isolated from a wide variety of tissues and, in general, their differentiation potential may reflect the local environment. They lack tissue-specific characteristics but, under the influence of appropriate signals, can differentiate into specialized cells with a phenotype distinct from that of the precursor. It may be that stem cells in adult tissues are reservoirs of reparative cells, ready to mobilize and differentiate in response to wound signals or disease conditions. Little information is currently available about the biology of endogenous stem cell populations in adults and their precise role in tissue repair or regeneration. This may be due in part to the lack of useful cell-specific markers. What is clear, however, is the ease with which these cells can be isolated and expanded in culture through many generations, while retaining the capacity to differentiate. Recent progress in the isolation and characterization of these cells has led to the development and testing of therapeutic strategies in a variety of clinical applications.

Mesenchymal stem cells (MSCs), which reside within the stromal compartment of bone marrow, have the capacity to differentiate into cells of connective tissue lineages, including bone, fat, cartilage and muscle. In addition, they play a role in providing the stromal support system for blood stem cells in the marrow. MSCs represent a very small fraction, 0.001�0.01% of the total population of cells in marrow. However, they can be isolated and expanded with high efficiency, and induced to differentiate to multiple lineages under defined culture conditions. These cells have generated a great deal of interest because of their potential use in regenerative medicine and tissue engineering. Both pre-clinical and clinical studies offer dramatic examples that illustrate the therapeutic value of MSCs. While the therapeutic testing of these cells has progressed well, there are still many questions to be addressed concerning the role of endogenous populations of stem cells in the adult, and the function of various stem cell niches. In addition, there are several aspects to the implanted cell-host interaction that need to be addressed as we attempt to understand the mechanisms underlying these therapies.


Frank Barry PhD, Scientific Director, Regenerative Medicine Institute, NUIG

Frank Barry is the Scientific Director of REMEDI. His area of research is in the therapeutic application of adult stem cells, especially mesenchymal stem cells (MSCs) from bone marrow. For ten years, he has directed research programmes focusing on the isolation and characterization of adult stem cells, and on the development of methods for their delivery in a variety of clinical indications. This has included cardiovascular and arthritic diseases. He has also developed approaches for the use of MSCs for the delivery of specific therapeutic genes, for example in rheumatoid arthritis. In addition, he has an interest in proteomics and mass spectrometry for the identification of surface molecules on cells. He has worked both in academia and in industry, and for the past ten years worked as a Research Director in the biotech sector in the US. He has been involved in the development of novel stem cell therapies and has directed programmes from early laboratory research and proof of concept, through preclinical evaluation, regulatory submissions and development of a clinical programme. He has also directed third level courses in Biochemistry, Biotechnology, Stem Cell Biology and Tissue Engineering in Ireland and the US.

Although early pre-clinical and clinical data demonstrate the safety and effectiveness of MSC therapy, there are still many questions to be answered surrounding the mechanism of action. Additional information is required concerning the therapeutic efficacy of transplanted cells and the mechanisms of engraftment, homing and in vivo differentiation. There is also a need to carry out appropriately designed toxicology studies to demonstrate the long-term safety of these therapies. The widespread use of stem cell therapy will also depend upon the availability of validated methods for large-scale culture, storage and distribution. In addition, there is a need for novel engineered devices for tissue-specific delivery of cells, such as cell-coated stents and catheter-based delivery in cardiovascular applications, and arthroscopic delivery in the treatment of joint disease. As these areas are addressed, new applications will be developed leading to novel therapeutic opportunities. Much has been learned about stem cell therapy in the past few years, and much remains to be learned.

Contact: Dr Frank Barry, Scientific Director, Regenerative Medicine Institute,
National Centre for Biomedical Engineering Science, National University of Ireland, Galway;
Tel: +353-(0)91-512636; Fax: +353-(0)91-750-596; E-mail: [email protected]