CRM researchers have pinpointed a key enzyme that is vital for the production of all blood cells in the body.
The enzyme is essential for the survival of specialised stem cells that give rise to and replenish the entire blood system with new blood cells, the study found.
The study team says the findings could help to improve the success of stem cell therapies that are being developed to treat some blood cancers and disorders of the immune system.
Scientists focused on an enzyme known as fumarate hydratasese, which is known to play a key role in the generation of energy inside cells.
A rare and fatal childhood disease caused by a deficiency in this enzyme has helped the scientists to identify its importance in the blood system.
To mirror human disease in mice, researchers deleted fumarate hydratase from blood cells in the animals. The mouse study found that deletion of fumarase from blood cells causesd blood stem cell failure and major defects in new blood cell production.
These defects could be traced back to defects in the specialised stem cells that give rise to new blood cells.
Blocking the enzyme causes a molecule called fumarate to build up inside the cells, which has wide-ranging toxic effects.
The study sheds new light on the conditions that blood stem cells need to survive, which could help to boost the success of stem cell therapies, the researchers say.
Professor Kamil R Kranc, CRUK Senior Research Fellow at the MRC Centre for Regenerative Medicine, said:
“Stem cell metabolism is an emerging field of research with an immense therapeutic potential. In future, we hope to identify the biochemical pathways affected by fumarate in stem cells and, by manipulating these pathways, improve the success of stem cell transplantation therapies.”
Scientists from the Medical Research Council (MRC) Centre for Regenerative Medicine at the University of Edinburgh led the study. The research is published in the Journal of Experimental Medicine and was funded by The Kay Kendall Leukaemia Fund, Cancer Research UK (CRUK), Bloodwise, Tenovus Scotland and Wellcome Trust.