Transplantation of hematopoietic stem cells (HSCs, the cells that can give rise to all blood and most immune cell types) can save patients whose own hematopoietic system is defective or has been destroyed (often through radiation or chemotherapy of cancer). HSCs are very rare, and it is often hard to obtain enough of them for a successful transplant. To overcome this limitation, Hans-Peter Kiem and colleagues have developed a way to expand HSCs in the laboratory prior to transplantation. As they report in the international open-access journal PLoS Medicine, expression of a gene called HOXB4 can instruct stem cells to divide and make more stem cells. When the researchers tested those expanded cell populations in monkeys that had received a lethal dose of radiation, they found that they 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 cord blood, which is harvested from the umbilical cord at birth. 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. Consequently, researchers are looking for ways to expand HSCs prior to transplantation. HOXB4 is known to be involved in stem cell maintenance and had shown some promise for stem cell expansion in mice. To investigate the potential of HOXB4 treatment for HSC expansion before transplantation in humans, Kiem and colleagues therefore turned to nonhuman primates, an established preclinical model for HSC transplantation and gene therapy.

The team showed that HOXB4 over-expression in populations of cells enriched for stem cells (i.e. those that are used for transplantation) for 6-9 days prior to transplantation greatly improved their subsequent engraftment in monkeys whose hematopoiet
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Contact: Andrew Hyde
ahyde@plos.org
44-122-346-3330
Public Library of Science
1-May-2006

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