Pluripotent stem cells offer huge opportunities in the field of regenerative medicine.
Red Blood Cells from Pluripotent Stem Cells.
Our approach involves culturing human pluripotent stem cells (PSCs) – both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) – in conditions similar to those in the human body to trigger their development towards red blood cells.
We have developed a protocol that alllows the production of cells that meet good manufacturing process guidelines required for clinical use. (Jo Mountford). This process can be used to produce red blood cells from both ESCs and iPSCs
Our current work aims to better understand the molecules and pathways involved in red blood cell production and maturation that will ultimately help us make the culture process more efficient. This will also help improve the final stage of red blood cell production – when the fully mature red blood cell expels its nucleus. This enucleation step does not currently happen efficiently in our culture system.
Red cells from multi-potent adult stem cells.
Our team has also developed a scalable, suspension-based process to produce red blood cells from adult blood stem cells (Dave Anstee).
These early blood cells – also known as haematopoietic progenitor cells – can be isolated from adult bone marrow or peripheral blood. Unlike red blood cells derived from pluripotent stem cells, red blood cells derived from adult blood stem cells do enucleate in culture with high efficiency.
We are applying the knowledge gained from how these cells enucleate to improve enucleation rates in red blood cells produced from pluripotent stem cells.
Experts in bioinformatics are comparing proteins and environmental signals in the different cells to identify key triggers in red blood cell maturation. Some of these are likely to be transcription factors that act as molecular “switches” during cell differentiation (Cedric Ghevaert and Jan Frayne).
Genome editing tools have been developed within our project that will allow the integration of these factors into specific chromosomal locations in pluripotent stem cells (Lesley Forrester).
We are also developing stem cell lines that carry fluorescent proteins tagged to transcription factors that will allow us to monitor the differentiation of pluripotent stem cells into red blood cells (Lesley Forrester). This will enable the screening of small molecules that increase differentiation rates (Jo Mountford).