Edinburgh Cancer Research

Blood study insight could improve stem cell therapy success

Researchers have pinpointed a key enzyme that is vital for the production of fresh blood cells in the body: May 2017

News 5.2017 Fh1 figure
Embryos lacking fumarate hydratase (Fh1) have multiple haematopoietic defects. Fh1 knockout embryos and their foetal livers appear pale indicating severe anaemia. Top panels: Control and Fh1 knockout embryos. Bottom panels: foetal livers from Control and Fh1 knockout embryos.

The enzyme is essential for the survival of specialised stem cells that give rise to new blood cells, the study found.

Experts say 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 called fumarase, which is known to play a key role in the generation of energy inside cells.

Children with gene mutations that affect fumarase have blood defects, which prompted researchers to investigate its function.

Major defects

The mouse study found that deletion of fumarase from blood cells causes 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.

Stem cells

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.

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 transplant therapies.

Professor Kamil KrancCRUK Senior Research Fellow, MRC Centre for Regenerative Medicine, University of Edinburgh

The research was prompted when researchers noticed that children with genetic mutations in the fumarase gene have blood defects.

Scientists from the Medical Research Council 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, Bloodwise, Tenovus Scotland and Wellcome.