Diseases of the blood system such as leukaemia and anaemia are often treated using cell therapies such as bone marrow transplantation and blood transfusion. However these procedures are reliant on a limited donor supply and are complicated by transmissible infections. The long term goal of our research is to replace these procedures with haematopoietic stem cells and red blood cells that have been produced in the laboratory from pluripotent stem cells. We are studying the molecular processes involved in the production of blood cells from pluripotent stem cells so we can optimise the production of cells with the appropriate function.
Protocols have been developed that allow the production of blood cell lineages from human pluripotent stem cells but it has not been possible to produce fully functional cells in sufficient quantities for therapeutic use. Erythrocytes produced from human pluripotent stem cells in vitro, for example have an immature phenotype; they express foetal, not adult globin and they fail to enucleate efficiently. Furthermore it has proven particularly difficult to produce fully functional haematopoietic stem cells that are capable of reconstituting the entire haematopoietic system from human pluripotent stem cells in vitro. Our aim is to improve the efficiency of blood cell lineage production in vitro using the following approaches:
- “Forward programming” cells by overexpression of key transcription factors at define time-points during the in vitro differentiation process.
- Production of reporter human pluripotent stem cells lines that mark the expression of these key transcription factors to allow high throughput monitoring of modified differentiation protocols.