Materials exploitation of the biointerface to control MSC quality and niche phenotype

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We understand that stem cells hold the key to curing many degenerative conditions. Currently lacking, however, are the technologies that will open up use of stem cells for regenerative therapies. In the body, in their niches, adult stem cells are controlled by their environment - a complex mixture of proteins, sugars and other cells. This environmental control allows stem cell growth with maintenance of stem cell phenotype (the cells observable characteristics). However, when we take stem cells out of the body and grow them in the lab they don't have these environmental controls and so quickly loose stem cell characteristics, making it hard to grow large numbers of clinically useful stem cells.In this project we will refine a material that we use to arrange proteins and cells in a particular way to allow stem cell growth. First, we will investigate mesenchymal stem cells (MSCs) from bone marrow. MSCs are responsible for provision of bone, cartilage, ligament and tendon cells. We will improve on our ability to grow these cells in the lab and will understand how the cells regulate themselves so that we can identify drugs and drug targets that we can exploit to improve growth in larger-scale stem cell cultures. Further we will develop our technology to allow culture without animal products so that the cells are clinically relevant for use in humans. However, in this project, rather than investigating MSC use in skeletal regeneration, we wish to see if we can maintain their ability to modulate the immune system for longer. MSCs have exciting potential to be used almost as a drug along with transplants as they can modulate immune responses to help prevent transplant rejection. The blood transfusion service are investigating this possibility and we will work with them using our approaches to expand high quality MSCs with immune modulatory capacity retained. Further, we will use our materials systems to investigate haematopoietic stem cell (HSC - stem cells that make blood cells) maintenance. In the bone marrow, HSCs stick to MSCs and this preserves their stem cell characteristics. In the lab HSCs don't proliferate and rapidly loose their stem cell phenotype. HSCs are important as they are central to a widely used stem cell therapy - the bone marrow transplant that remains a successful tool in the fight against conditions such as leukaemia. In leukaemia, HSC progeny cells that go on to make blood cells (red blood cells that carry oxygen around the body and white blood cells that fight infections) become diseased. Thus, bone marrow, that contains stem cells, can be moved from a healthy donor to a recipient who has had their own, diseased, stem cells killed. The donated stem cells have the ability to repopulate the blood of the recipient with disease free cells. This is an amazing example of the ability of a few stem cells to repopulate and regenerate.There are, however, some major drawbacks. Firstly, this is a one donor to one recipient therapy and the ability to match recipients with tissue-matched donors is very limited. While there have been advances, such as use of mobilised peripheral blood stem cells, supply still falls far short of demand and this severely limits the therapy that can be offered.While it is very ambitious to say that we believe our technology can be used to grow HSCs in the lab, we believe we can take the first steps towards this. Our aim is to bioengineer niche environments using MSCs and our novel materials. By controlling the characteristics of the MSCs we will increase the number of HSC sticking to them. This achieved, we will investigate HSC phenotype maintenance and look for the tempting possibility of HSC growth.Understanding stem cells and unlocking their potential is one of the major challenges of this century. This project aims both to improve understanding and unlock potential.