Zhang used a microarray platform to search for genes that were active in these newly discovered cells, but not active in similar neighboring cells. Some such genes, he reasoned, might encode secreted proteins that sustained stem cells. Eventually, he located a number of such genes.
In the fall of 2003 and early 2005, Zhang reported in the journal Blood how one of these genes codes for a growth factor protein called IGF-2. When Zhang purified IGF-2 and added it in a solution to hematopoietic stem cells that he had isolated, the stem cells increased eight-fold in number.
Zhang then discovered that two more growth factor proteins, Angiopoietin-like 2 and ?, abbreviated as angpt12 and angpt13, were also abundantly expressed in these stem-cell supporting cells. When Zhang combined these two proteins with IGF-2 and added them to hematopoietic stem cells, the result was a 30-fold increase.
"People have been culturing and working with these cells for years, and never before have we seen such an increase," says Zhang.
A 30-fold expansion, if replicated in human cells, could open up a number of doors for researchers working on adult stem cells. Currently, patients with certain blood diseases are treated with stem cells. These stem cells can be acquired either from a donor's bone marrow, or even from cord blood (donated cord blood, or the patient's own). Still, in both these cases, the actual number of stem cells from a donor often falls short of the number needed to adequately treat the patient. This technique could directly address this problem.
Gene therapy is another area where these findings can be of immediate value, Lodish says.
With gene therapy, a genetic defect is corrected by administering a healthy version of the gene into a patient. For example, a physician isolates hematopoietic stem cells from a patient, introduces a harmless virus into them that expresses a correct version of the m
Source:Whitehead Institute for Biomedical Research