Our bone marrow harbours an essential collection of immune cells that help to keep us healthy. Research in Dublin which focuses on one particular cell type could lead to new treatment possibilities for diseases involving the marrow.
The cells in question are known as Natural T-cells (NT cells). They have an essential role to play in directly attacking infectious or cancerous cells by themselves or by prompting other immune cells to attack.
Their discovery occurred in the late 1980s and since then there has been intensive international study of these cells. Mr Jonathan Dean of the Education and Research Centre at St Vincent's Hospital and the Department of Pharmacology at University College Dublin is involved in this effort. In particular he is studying where in the body these cells can be found. He is also detailing the biochemistry of the cells.
Mr Dean presented his research at the annual Merville Lay Seminars at UCD earlier this month and took first prize. The Seminars had been planned for March but the Foot and Mouth outbreak caused their delay. The judging panel, chaired by Mr Fergus Finlay, heard six student research presentations and chose Mr Dean's as the best of the group.
"The thrust of the work is to look at these particular cells in their normal pattern and their pattern with malignancy," Mr Dean explained. It also involves an analysis of chemical messages released by NT cells and their ability to attack and kill cancer cells.
Our understanding of NT cells is still in its early stages, he said. "It is still a fishing expedition." A clearer picture of their role in defending against cancer opens up at least two potential clinical possibilities, he stated.
The first is to identify any relationship between changes to NT cells and the occurrence of blood cancers. This could define possible treatments for cancer on the basis of NT cell condition.
A more radical possibility would be to "harvest" NT cells so they could be cultured in vitro and then reintroduced to fight cancers. "You would either enrich their number or persuade them to act more vigorously, then you can actually use them as a tool in the therapy," Mr Dean said.
A third year Ph.D. student, Mr Dean's work is funded by the Cancer Research Advancement Board, a subsidiary of the Irish Cancer Society and by Enterprise Ireland. It is overseen by the director of the St Vincent's Hospital centre, Dr Cliona O'Farrelly.
A key to any successful harvesting of cells would be to find where they live. Work with mouse models showed that NT cells were plentiful in both the liver and bone marrow. However, similar sampling in humans indicated that while found in high numbers in the human liver, bone marrow only seemed to contain a fifth as many NT cells as expected. Mr Dean set out to discover whether the NT cells might be "hiding" in the marrow.
The standard sampling method involves "bone marrow aspiration" in which a thin needle is inserted into the marrow and a liquid sample drawn off. This returned only low levels of NT cells. Mr Dean decided to try a "solid core biopsy" in which a sample of marrow and adjacent bone tissue is extracted from the top of the pelvis.
The space inside bones is like the inside of a Crunchie bar, he said. The bone forms a thin honeycomb structure and the marrow cells nestle in the spaces in between.
The core samples are chopped up and exposed to enzymes which digest the material that holds the cells together in the bone matrix. This eventually leaves the NT cells suspended in a liquid and very easy to count.
These samples delivered five times the NT cells found in the liquid samples, proving human marrow to be a key repository for these important blood cells.
Ongoing work now focuses on the characterisation of normal NT cells, looking at the marker proteins expressed on the cell surface. This will allow a detailed follow-on comparison of healthy versus diseased NT cells.