Human mesenchymal stem cells (MSCs) are found in adult tissues such as the bone marrow. They are able to divide to increase in numbers and to generate tissues including bone and cartilage. Therefore, MSCs may provide a valuable tool for the treatment of diseases that affect the skeleton, for example by helping to replace lost bone in osteoporosis. Another interesting property of MSCs is that they appear to be able to seek-out tumours and may be able to reduce tumour size, but the mechanisms involved are unclear.

In recent studies, we have identified new and exciting properties of MSCs that suggest that MSCs can be induced to have potent cancer-killing effects that may also be used to treat primary bone cancers. MSCs can be easily extracted from human bone marrow and are commonly grown on flat plastic surfaces. In our laboratory, we have established a novel culture system, where the MSCs are grown as three-dimensional (3D) spheres of cells (or "3D MSCs"). Through extensive analyses, we have found that this 3D culture method changes the behaviour of MSCs remarkably. Most noticeably, we have shown that 3D MSCs produce a factor (called IL-24) that can selectively kill certain cancer cells without affecting normal cells. The levels of IL-24 in 3D MSCs are 300 times higher than those found in MSCs grown normally on plastic. The application of IL-24 has reached phase I clinical trials as a treatment for some cancers. However, the therapy requires the use of viruses to introduce IL-24 and maintain high enough levels of IL-24 to have an effect, and viruses have their own safety concerns.

This proposal will determine if 3D MSCs can also be used to selectively target osteosarcoma and Ewing's sarcoma cells whilst having no detrimental effects on healthy bone cells. We will identify how the IL-24 produced by 3D MSCs is able to kill the cancer cells; this is important to confirm the mechanism of action. The work will help us to understand if 3D MSCs may be used in the future for treating primary bone cancers. If successful, the advantages of this type of treatment are that:

The concept of using MSC therapy has already been shown to work in treating other illnesses.

We can make use of the ability of MSCs to home to tumours to provide a precise delivery.

IL-24 selectively targets cancer cells and does not damage normal cells like some conventional cancer therapies.

The treatment can be achieved using a cell-based procedure without the need for viruses.

Dr Paul Genever, University of York