Use of bioactive polymers to regulate differentiation of embryonic stem cells in three-dimensional bioreactors

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Human embryonic stem (hES) cells, isolated from very early stage embryos, are able to become any cell in the body and have great potential for the treatment of many serious diseases. However there is a practical problem in producing a sufficient number of hES cells to treat human diseases, such as heart disease and cancer. At present hES cells must be grown under specialised conditions as a 2-dimensional (2-D) culture. This severely limits the number of cells that can be obtained and our project will allow the culture of hES cells in 3-dimensions (3-D). To allow you to appreciate the significance of 2-D and 3-D growth of hES cells, imagine how many more tennis balls you could squeeze into your living room compared to those you could only place on the floor. The bigger the volume of the room the more tennis balls you can fit in, irrespective of the area of the floor. Therefore, 3-D growth of hES cells allows us to grow a lot more cells than we can at the present time. However, it's not that easy! If we grow hES cells in 3-D they will either die or turn into other cell types (called differentiation) therefore we need to stop them from differentiating. We will use two methods to stop the hES cells differentiating in 3-D culture. First we will use sugars. These are different to the sugar you put in your coffee since they consist of a long chain containing areas that can regulate biological activities. All the cells in your body naturally contain these sugars and they are very important in maintaining healthy and viable cells. Basically, we will use these sugars to help keep the hES cells feeling well in 3-D culture. The other method we will develop uses oligopeptides. All proteins in your body are made up of amino acids and an oligopeptide is simply a chain of amino acids. Like sugars, peptides can regulate what happens in your body. We will use oligopeptides that make hES cells healthy and allow them to grow in 3-D culture. Sugars and oligopeptides can work well together and we hope that by combining them together we can make the hES cells grow very well in 3-D. In this way we will engineer bioreactors of cells in 3-dimensions that can produce large numbers of hES cells. This will allow us to provide a new technology for mass production of hES cells and then turn them into specific cell types that may help to treat patients with serious diseases.