New method for multiplying stem cells

US researchers have discovered how to expand a population of blood stem cells growing in the laboratory, a finding that offers hope for patients requiring bone marrow transplants. It also holds promise for some gene therapy treatments, say the team, who are based at the Whitehead Institute in Cambridge, Massachusetts. The study, published early online in the journal Nature Medicine, shows that by using a 'cocktail' of growth factors, it is possible to multiply a population of mouse blood stem cells by 30 fold. The scientists are now hoping to repeat their results with cells from human cord blood.

Blood stem cells, present in bone marrow and umbilical cord blood, have been successfully used to treat a range of different blood disorders. However, their use is limited because the number of stem cells is often insufficient to treat the patient. This is particularly true of blood obtained from a single umbilical cord, which does not contain enough stem cells to treat an adult.

Previous research by the Whitehead group identified liver cells in the mouse fetus that interact with blood stem cells. The team found that these 'stem-cell supporting cells' produce a growth factor called IGF-2 - which, when added to blood stem cells, triggers an eight-fold increase in their number. In the latest study, the researchers discovered that the liver cells also make two other crucial growth factors, called Angiopoietin-like 2 and 3 (angptl2 and angptl3). Adding a cocktail of all three growth factors to the blood stem cells upped their numbers by 30 fold, the team report. 'People have been culturing and working with these cells for years, and never before have we seen such an increase', said lead author Cheng Cheng Zhang.

If the findings can be replicated with human blood stem cells, then the method could eventually be used clinically to increase the numbers of cells used in bone marrow transplants, which can be used to treat diseases such as leukaemia and other blood disorders. The study also helps basic research into stem cells, aimed at finding out how stem cells produce other, more specialised types of cell.

The authors say the technique could also be used in some gene therapy treatments, which involve inserting a working gene into blood stem cells taken from a patient. Several patients with hereditary blood disorders have been successfully treated using this approach, but three patients in a French trial developed leukaemia, triggered by the virus used to deliver the gene. Increasing the number of cells would allow doctors to make extra safety checks, say the researchers: 'If, before the stem cells have been reintroduced into patients, the physicians could first multiply them in the lab, they could then run assays determining if the virus has landed in any undesirable places', explained team leader Harvey Lodish.