Award for arthritis treatment discovery

TCD's Dr Daniel Kelly has won the President's €1 million Young Researcher Award for his study of stem cells used to create replacement cartilage for arthritic joints

NEW TREATMENTS for arthritis could emerge from a study of how stem cells react to the complex mechanical forces within knee, hip and other joints. The work could see the development of replacement cartilage grown outside the body and then implanted in ailing joints.

Dr Daniel Kelly leads the work in Trinity College Dublin's Centre for Bio-engineering. He is also the 2008 recipient of the President of Ireland Young Researcher Award, announced last month at Aras an Uachtaráin, funded by Science Foundation Ireland (SFI) and worth almost €1 million.

Kelly is already a principal investigator at the centre, with previous funding awards from SFI, Enterprise Ireland, and the Irish Research Council for Science, Engineering and Technology's Embark programme.

He currently heads a team of seven, with an ambitious research goal being no less than the repair of cartilage in joints caused by injury or diseases such as arthritis. This research direction arose during Kelly's PhD programme at Trinity, where he studied natural "osteochondral defect repair".

Cartilage is the essential tissue that cushions the ends of bones that meet in joints. Cartilage is lost in arthritis, causing inflammation and pain when the bone ends rub against one another.

Holes sometimes appear in the protective cartilage, damaging the bone but also initiating a natural repair mechanism, explains Kelly. Adult stem cells from the bone marrow are released into the joint and these then change or "differentiate" into replacement cartilage that repairs the hole.

"My PhD looked at what effect the mechanical forces inside the joint had on the differentiation of these cells," he says.

The cells in question, mesenchymal stem cells (MSCs), can change into a variety of tissues such as cartilage but also fibrous connective tissue, muscle and even bone.

His contention is that the "mechanical environment" produced by a joint under normal stresses and strains is central to the regulation of how the stem cells differentiate into cartilage.

He carried this work forward when he returned to Trinity's School of Engineering where he lectures in mechanical engineering. Earlier funding allowed him to build a team and now the President's award will help him make considerably more progress towards explaining these complex processes.

He has already produced detailed computational models that describe the mechanical forces exerted inside a joint, using a common engineering approach called "finite element analysis".

He has now also built a number of bioreactors that will allow him to study how living stem cells respond to mechanical forces, data which can be compared with the results of his computational work.

This involves recovering MSCs from the bone marrow and then growing them up in bioreactors. Animal MSCs are currently under study, but Kelly hopes to acquire and use human cells for this work.

The bioreactors nourish the MSCs but can also exert different forces on them to approximate the stresses that exist within the joint. One bioreactor squeezes the cells between flat plates, and another exerts hydrostatic forces on the cells. A third uses "fluid profusion", a stream of fluid that stresses the cells.

"The main reasons for doing this is, first, to try and understand how the stem cells will react and what effect the mechanical forces will have on differentiation and on the character of the produced and, second, to assess the quality of the replacement tissue," Kelly says.

Kelly describes the work as "functional tissue engineering". Putting the cells under true-to-life mechanical forces will also help him decide whether it is better to place a layer of stem cells under direct stress or whether they will perform better if seeded onto some type of scaffold.

"If the mechanical environment is indeed controlling the differentiation we can tailor the scaffolds to control this," he says.

An intriguing possible result is that a scaffold would be produced and then seeded with MSCs and then either put under stress in a bioreactor or surgically inserted directly into a joint where the natural mechanical forces can cause the expected differentiation.

This is a highly complex study, but one that holds particular promise, Kelly suggests. If treatments can indeed be produced they will most likely initially be used to repair damage caused by sports injuries. In time, however, they might prove useful in renewing joints damaged by arthritis.