Identifying the skeletal stem cell for regeneration: harnessing smart nanoparticles and single cell DropSeq molecular profiling platforms

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We are now living much longer than we used to. These are exciting times in medical research and indeed, medical advances have led to a welcome increase in life expectancy. However, an unfortunate consequence of this is that as we reach later life the chances that we can become ill or injured increase dramatically. One big problem that elderly people face is illness and injury associated with the bones and joints. Diseases like osteoporosis and arthritis cause pain, cause bone fractures and lead to immobility and distress to tens of thousands of people each year, costing the taxpayer tens of millions of pounds (in the UK there are some 150,000 osteoporosis-associated wrist, spine and hip fractures, with an estimated healthcare cost of £1.7 billion per annum). So new treatments that enable the skeleton to heal better are urgently required. Cell-based therapies are currently some of the most exciting and promising areas for bone disease treatment and reparative medicine. However, despite intensive research interest there are currently no reliable methods to isolate (or enrich sufficiently) the rare bone stem cells (known as skeletal stem cells) needed for these strategies. Thus, it is critical that new technologies be generated to enable the robust isolation of bone stem cells from patients (from their bone marrow) for clinical use. We propose that new approaches, which combine stem cell biology with the latest approaches to identify and cells together with innovative statistical methods will allow us to enrich and isolate the bone stem cell. In this unique programme of work we will be able, for the first time, to use very small (nanoscale) probes to further refine our cell selection and identification strategy. In particular, we will combine a novel single cell identification procedure (which produces a "barcode" for each cell) with unique cell sorting devices to allow us to isolate bone stem cells. We will combine the unique bar codes (derived from the molecular (RNA) machinery) in the individual cells in combination with the smart nano-probes to allow us to tag cells that will separate and examine if they are stem cells and their ability to make bone and cartilage. Through this unique approach we will enrich for bone stem cells that we will characterise and examine if they are stem cells and test their ability to make bone and cartilage.This exciting programme of research offers the ability to isolate the bone stem cell and provide substantially enriched, and potentially pure populations of bone stem cells. This will advance considerably our understanding of bone stem cell basic biology and offer significant therapeutic impact for bone repair and the treatment of bone disorders in our ageing population.