Collagen (I) homotrimer in age-related fibroses and tissue degeneration: evaluation as a stem cell biomarker

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Collagen is the most abundant structural protein in the body. Collagen creates an environment within which cells reside and forms fibres that make tissues resilient to external stresses, for example during mechanical loading such as that occurs during normal locomotion. Collagen can be broken down and reformed by cells using biological enzymes; a normal process during growth and development. However, cancer cells invade tissues by degrading collagen whilst concurrently making their own non-degradable version of collagen, thereby creating a pathway for invasion. Non-degradable collagen has also been found in degenerative skeletal diseases such as osteoarthritis and osteoporosis as well as in fibrotic diseases including liver cirrhosis. The only other reports of non-degradable collagen are from embryonic cells or tissues, indicating that it might be produced by a type of stem cell and fulfil a normal biological function. Stem cells have the potential to form many different tissue types and their use has the potential to revolutionise approaches to regenerative medicine and tissue engineering. Embryonic stem cells can form all cell types in the body, but their use in research and in treatment trials is limited because of ethical considerations. Adult tissue stem cells are rare and may only be able to regenerate the tissue that they came from, but they could potentially be used to treat the patient from which they were isolated without subsequent immune rejection. The aim of this project is to determine whether non-degradable collagen is produced by embryonic and/or adult stem cells and to understand how cells control the genes responsible for this type of collagen production. This project will investigate how ageing affects the expression of these two forms of collagen and might predispose to disease. This research is important to characterise stem cells and to understand their role in the repair and regeneration of collagen-rich tissues. A clearer understanding of the role of particular types of collagen in ageing and disease would allow the development of biological markers for age- and disease-associated collagen. Such biological markers could be incorporated into tests to determine an individual's likelihood of developing diseases such as cancer, arthritis or osteoporosis. They could also be used to predict how quickly an individual might become frail and immobile in old age and to therefore tailor lifestyle recommendations (diet, exercise, built environment) and future anti-ageing medicines for particular groups. The results from this project would be informative for research programs that aim to use stem cells for transplantation or in tissue engineering.