HSCI researchers at the Massachusetts General Hospital Center for Regenerative Medicine have a developed a new type of human pluripotent stem cell that can be manipulated more readily than currently available stem cells. As described in the latest edition of Cell Stem Cell, these new cells could be used to create better cellular models of disease processes and eventually may permit repair of disease-associated gene mutations.
“It has been fairly easy to manipulate stem cells from mice, but this has not been the case for traditional human stem cells,” explains HSCI principal faculty member Niels Geijsen, PhD, who led the study. “We had previously found that the growth factors in which mouse stem cells are derived define what those cells can do, and now we've applied those findings to human stem cells.”
In their previously published work, Geijsen and his colleagues demonstrated that the growth factor conditions under which stem cells are maintained in culture play an important role in defining the cells’ functional properties. Since the growth factors appeared to make such a difference, the researchers tried to make a more useful human pluripotent cell using a new approach. They derived human induced pluripotent stem (iPS) cells in cultures containing the growth factor LIF, which is used in the creation of mouse ES cells. iPS cells are created by reprogramming adult cells and have many of the characteristics of human ES (embryonic stem) cells, including resistance to manipulation.
The resulting cells visibly resembled mouse ES cells and proved amenable to a standard gene-manipulation technique that exchanges matching sequences of DNA, allowing the targeted deactivation or correction of a specific gene. The ability to manipulate these new cells depended on both the continued presence of LIF and expression of the five genes that are used in reprogramming adult cells into iPS cells. If any of those factors was removed, the cells reverted to standard iPS cells.
“Genetic changes introduced into [the cells] would be retained when they are converted back to iPS cells, which we then can use to generate cell lines for future research, drug development, and, someday, stem-cell based gene-correction therapies,” Geijsen said.