Cell interactions in an adult mesenchymal stem cell niche

Mesenchymal stem cells (MSCs) are stem cells that cant form different types of cells derived from mesenchyme. These include bone cells, cartilage cells, fat cells and many others. MSCs are found in several adult tissues, most notably the bone marrow. In addition to their stem cell properties, MSCs also have a well-established ability to repress the immune system. MSCs are thus a very important source of cells for clinical applications in tissue repair and in immune suppression and several large clinical trials are underway in the US. The problem with MSCs is that most research has been carried out on the bone marrow, a difficult tissue to study and the main source of MSCs for clinical applications is the bone marrow or fat tissue. In order understand more of these cells so that they use in clinical applications can be improved, a more accessible source of cells needs to be studied.
MSCs are also found in teeth, particularly in the pulp tissue in the centre of the tooth where they are involved in tooth repair following damage. Commercial banking of tooth pulp cells from naturally lost children?s teeth is available. However in common with bone marrow MSCs these cells are difficult to study since they are present in very small numbers.
Unlike us, mice have teeth (incisors) that grow continuously because they have a population of MSCs that continuously provide new cells. We have identified the location of these cells and can visualise the cells easily. This means we now have a large population of easily accessible MSCs that can be studied in detail to understand their properties and how they are maintained as stem cells. This information will greatly benefit the understanding of other MSCs and improve the use of these cells in clinical treatments.

Understanding the properties of mesenchymal stem cells (MSCs) and their niches is a fundamental goal in stem cell biology. Rodent incisors are able to grow continuously as a result of having separate mesenchymal and epithelial stem cell niches that provide sources of cells to replace those lost from the tips of the teeth as they wear. We have identified the location of the MSCs in mouse incisors that can be easily visualised from the expression of polycomb complex (PRC1) and associated genes and our aim is to use this niche as an experimentally accessible model to study the properties of dental MSCs and their niche. Mouse genetic, embryological, biochemical and in vitro culture approaches will be used to investigate:

1. Novel genes expressed in the MSC niche
2. Control of the differentiation of MSCs
3. The role of perivascular cells in maintaining the MSC niche
4. The role of polycomb proteins (PRC1) and PRC1 interacting protein, Bcor in the MSC niche, self-renewal and differentiation
5. Identification of PRC1 protein target genes