Development of nanopatterned substrates for the delivery of high quality stem cells

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The use of stem cells in regenerative medicine holds great potential and with an increasingly aging population, we need to look for new opportunities. Their potential use span from orthopaedic applications such as arthritis and osteoporosis to neurodegenerative disorders such as Parkinson's and Alzheimer's, to name a few. The body has a constant source of stem cells located in niches within the body. From a scientific and clinical point of view, one of the most exploited sources for adult stem cells is the bone marrow. The bone marrow is relatively easy to access and stem cells can be easily isolated from the extracted cell population.However, until recently, a major hurdle is that the stem cells cannot be cultured for extended periods in culture and maintain their regenerative potential (multipotent). The very potential of stem cells, that they can change into many different cell types and so help repair damage on demand, means that their profile (phenotype) is unstable in culture. Hence, as we culture stem cells they soon lose the very potential and potency we want to exploit. We have recently (2011) demonstrated that by culturing the cells on a uniquely nanopatterned surface (nanopits, 100 nm in diameter and 100 nm deep, arranged in a square lattice) it is indeed possible to keep the cells in the multipotent state in prolonged culture as well as expand the number of cells.These nanopatterned surfaces resemble the tracks on a Blu-Ray disc and indeed our technology is very similar to the production of optical media where nanopatterns can be injection moulded into polymer discs in high volumes and at a very low cost. We can change the arrangement of the nanopatterns, thereby tuning the stem cell response to growth without profile (phenotype) drift and to target desired changes to tissues we want (known as differentiation). This is has important implications on the design of implants (like a hip replacement implants) where a specific cell changes (differentiation) is desirable. An example of this is again, orthopaedic implants where differentiation of cells to bone is desirable, or an area with perhaps even more potential is the growth of large numbers of stem cells. Thus, a key research goal is to take a patient's stem cells, grow them in the laboratory to useful numbers, and then place them back into the patient to spark regeneration. Scale up of our technology will allow this. The technology we have used so far has only allowed us to explore the stem cell interaction to a very limited number of different geometries (<10). In this proposal we will develop a new platform where a single sample will contain 1000 different patterns thereby allowing us to investigate a much larger library of nanopatterns and their ability to influence the fate of the stem cells. From these libraries new patterns will be identified and we will investigate them in more detail using mass spectrometry to identify small molecules influencing the cell fate.Importantly, to see real benefit of these discoveries, it is vital that we are able to scale the materials used to large areas to sustain the growth and expansion of stem cells used for regenerative medicine or pharma. As described above, our technology is very similar to the production of DVDs and Blu-Rays, which means that it lends itself to a cost effective mass production of the nanopatterned surfaces. To demonstrate this potential, we will expand extracted bone marrow stem cells to 5 million cells, the number of cells used for the fully tissue engineered trachea demonstrated in 2008.