The researchers have tested the expanded cell populations in monkeys that had received a lethal dose of radiation and found out that the cells were better at reconstituting the monkeys' immune and blood systems.

HSCs are found in small numbers in the bone marrow, the peripheral blood, and in umbilical cord blood. Cord blood is increasingly being used for transplantation, but the low number of HSCs present in a unit of cord blood means that transplanted cells can be slow to establish themselves (or engraft) in an adult recipient, prolonging the time the patient is susceptible to infections. Researchers are looking for ways to expand HSCs prior to transplantation. Kiem and colleagues have turned to nonhuman primates to investigate the potential of HOXB4 treatment for HSC expansion before transplantation in humans.

The team showed that HOXB4 overexpression in populations of cells enriched for stem cells for 6-9 days prior to transplantation greatly improved their subsequent engraftment in monkeys whose hematopoietic system had been destroyed through radiation. It was a proof-of-principle study that used small numbers of monkeys. Additional experiments are now planned to further test whether HOXB4 can eventually be used to improve the expansion and engraftment of stem cells in patients whose hematopoietic system has failed.

Kiem and colleagues achieved HOXB4 over-expression through introducing an active copy of the gene into the cells. However, because HOXB4 protein is available in recombinant form (i.e. produced in cell culture, much like human insulin), it should be possible to treat HSCs directly with the protein, avoiding the potential problems associated with genetic manipulation of the cells.