New gene-editing system enables large-scale studies of gene function.
MIT and Whitehead Institute researchers have discovered a way to multiply an adult stem cell 30 times, an expansion that offers tremendous promise for treatments such as bone marrow transplants and perhaps even gene therapy.
"A 30-fold increase is 10 times higher than anyone's achieved before," says MIT professor of biology and Whitehead member Harvey Lodish, senior author on a paper published Jan. 22 online in Nature Medicine.
Adult stem cells may be free of the ethical concerns that hamper embryonic stem cell research, but they pose formidable scientific challenges. Chief among these is the doggedness with which adult stem cells differentiate into mature tissue the moment they're isolated from the body. This makes it nearly impossible for researchers to multiply them in the laboratory. And because adult stem cells are so rare, it is difficult to use them to treat disease.
Chengcheng Zhang, a postdoctoral researcher in the Lodish lab, was determined to develop a way to multiply adult stem cells that had been isolated from tissue. Achieving this goal required some intricate laboratory sleuthing.
Zhang began by studying adult hematopoietic -- blood cell forming -- stem cells. Offspring of some of these cells develop into all of the red and white blood cells, while others form the immune system. Using fetal tissue from mice as the source of these cells, Zhang discovered a population of cells that were not stem cells, yet appeared to interact with stem cells, preserving and allowing them to multiply in the fetal environment.
When he isolated the stem cells in the lab and cultured them in a dish by themselves, they died. When he mixed them with these newly discovered cells, they thrived. But how did these new cells manage to sustain the stem cells so dramatically?
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.
Earlier, Zhang reported in the journal Blood that one of these genes codes for a growth factor protein called IGF-2. When Zhang purified IGF-2 and added it 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 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.
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.
This research was funded by the National Institutes of Health and the National Science Foundation.