Changing growth factors produce cells that should be more useful for research, future therapies
Wednesday, 09 June 2010
Researchers from the Massachusetts General Hospital Center for Regenerative Medicine (MGH-CRM) and the Harvard Stem Cell Institute 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 June 4 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 Niels Geijsen, PhD, of the MGH-CRM, 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."
LIF, which is used in the creation of mouse ESCs.
The resulting cells visibly resembled mouse ESCs 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 iPSCs. If any of those factors was removed, these hLR5- (for human LIF and five reprogramming factors) iPSCs reverted to standard iPSCs.
"Genetic changes introduced into hLR5-iPSCs would be retained when they are converted back to iPSCs, which we then can use to generate cell lines for future research, drug development and someday stem-cell based gene-correction therapies," says Geijsen. He is an assistant professor of Medicine at Harvard Medical School and a principal faculty member of the Harvard Stem Cell Institute.
A Murine ESC-like State Facilitates Transgenesis and Homologous Recombination in Human Pluripotent Stem Cells
Christa Buecker, Hsu-Hsin Chen, Jose Maria Polo, Laurence Daheron, Lei Bu, Tahsin Stefan Barakat, Patricia Okwieka, Andrew Porter, Joost Gribnau, Konrad Hochedlinger, Niels Geijsen
Cell Stem Cell, Volume 6, Issue 6, 535-546, 4 June 2010, 10.1016/j.stem.2010.05.003
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