Newton001: Characterisation of Adult Stem Cells and the initiation of an Adult Stem Cell Bank

Most adult tissues contain a population of stem cells called mesenchymal stem cells or pericytes, that are normally found surrounding capillaries. These stem cells can give rise to a number of different cell types, including cartilage and bone, that can be used to repair damaged or defective tissues in the body. The pericytes found in the head and neck, including those found within teeth, appear to be different to those of the rest of the body, and may be able to give rise to a wider range of different tissues, for example, nerve tissues, which makes them of interest in developing new treatments for a variety of diseases. We propose therefore to characterise in detail the pericytes found within teeth, in the dental pulp, as an example of those in the head and neck, and compare them with the pericytes found in other parts of the body. Fat is a very convenient source of pericytes since it contains a large number of these cells and is often removed surgically.
We will look at the overall pattern of genes which are expressed in these two populations of pericytes, to determine what the exact differences between them might be, and in parallel, we will compare the ability of the two types of pericyte to give rise to a range of different cell types that could be useful in the clinic, for example, bone, cartilage, muscle, nerves and pigment cells. If the two types of pericyte do show differences in the types of tissues they can produce, we will ask whether we can explain these differences based on any differences we observe in the patterns of genes expressed in these cells. The value of this is that around the world, scientists and clinicians are interested in creating banks of these pericytes, so that they are available when needed by any suitable patient. The pericytes obtained from fat are a very convenient source of cells to store in such banks, but if the pericytes from dental pulp are able to make a wider range of useful tissues, then we should clearly be including these cells in the bank in addition to those from fat.

Pericytes are adult stem cells of mesodermal origin, obtained in high yield from adipose tissue. Dental pulp contains a population of stem cells (DPSCs) that closely resemble pericytes but are derived from ectoderm of the cranial neural crest. This difference may allow DPSCs to differentiate more readily into glial cells, neurons and melanocytes. We will address two questions related to the clinical use of these adult stem cells. First, do pericyte subsets differ in the genes they express and how does this allow them to produce different tissues. Secondly, when establishing banks of adult stem cell, whether such banks should include both pericyte subsets.

What are the differences between neural crest and mesoderm derived pericytes?

We have analysed the expression profiles of adipose derived pericytes. We will use the same techniques to analyse DPSC to determine the differences between these two populations. RNA-seq analysis will be carried out at the MRC Centre for Regenerative Medicine, in Edinburgh. Proteomic profiling will be carried out at the Pontificia Universidade Catolica do Parana, in Brasil, while the analysis of this data will be performed jointly with the Edinburgh group.

Do such differences in expression profiles account for the differences in fate potential?

In this part of the program we will compare the differentiation of dental pulp and adipose tissue pericytes into osteoblasts, chondroblasts, myoblasts, neurons , glial cells and melanocytes. Expression profiling of the cultures would be carried out at different time points to determine what differences exist between the stem cells from different sources and how these determine the different outcomes.

The results of our study will determine the nature of the stem cells that should comprise adult stem cell banks - whether they may be restricted to adipose tissue derived pericytes or whether DPSC should be included to maximise the clinical applications of such banks.

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