HoxB4 is a homeotic gene whose expression in vivo has been shown previously to enhance HSC regeneration. Now, Jennifer Antonchuk, Guy Sauvageau, and Keith Humphries (Terry Fox Laboratory, Vancouver, BC) demonstrate that the number of adult HSC can be expanded in vitro when bone marrow cells are transduced with HoxB4. Compared with untransfected cells, the HoxB4- expressing cells showed a 40-fold net increase after 14 d in culture.
“So far, this [method] stands out uniquely as a means to expand stem cells,” says Humphries. “The stem cells are normal in terms of being able to differentiate, and still have a potent ability to regenerate stem cell compartments,” as shown by the ability of the in vitro–expanded cells to engraft in irradiated mice. The use of HoxB4- expressing cells could help prevent significant losses of the important HSCs in culture during gene therapy. Additionally, Humphries hopes the technique will improve treatments for the effects of chemotherapy and radiotherapy, by increasing the number of a patient's own stem cells that can be used for transplantation.
HoxB4 is also able to induce embryonic cells to become HSCs, according to a second publication by Michael Kyba, Rita Perlingeiro, and George Daley (Whitehead Institute for Biomedical Research, Cambridge, MA). Expression of HoxB4 in yolk sac cells or in embryonic stem cells led to the differentiation of these cells into mature blood cells. Additionally, the HSCs generated in vitro were able to engraft in both primary and secondary recipients. The signal transduction pathways induced by HoxB4 that lead to HSC expansion remain to be determined. ▪