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New type of human stem cell may be easier to manipulate

Date:
June 11, 2010
Source:
Massachusetts General Hospital
Summary:
Researchers have a developed a new type of human pluripotent stem cell that can be manipulated more readily than currently available stem cells.

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."

The first mammalian embryonic stem cells (ESCs) were derived from mice and have proven very useful for studying gene function and the impact of changes to individual genes. But techniques used in these studies to introduce a different version of a single gene or inactivate a particular gene were ineffective in human ESCs. In addition, human ESCs proliferate much more slowly than do cells derived from mice and grow in flat, two-dimensional colonies, while mouse ESCs form tight, three-dimensional colonies. It is been extremely difficult to propagate human ESCs from a single cell, which prevents the creation of genetically manipulated human embryonic stem cell lines.

In previous 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 cells (iPSCs) -- which are created by reprogramming adult cells and have many of the characteristics of human ECSs, including resistance to manipulation -- in cultures containing the growth factor 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 coverted 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.

Co-authors of the Cell Stem Cell paper are lead author Christa Buecker, MGH-CRM and Harvard Stem Cell Institute (HSCI); Hsu-Hsin Chen, PhD, Laurence Dahern, and Konrad Hochedlinger, PhD, MGH-CRM and HSCI; Patricia Okwieka, MGH-CRM; Jose Polo, PhD, MGH Cancer Center; Lei Bu, PhD, MGH Cardiovascular Research Center; Tahsin Stefan Barakat and Joost Gribnau, PhD, University Medical Center, Rotterdam, The Netherlands; and Andrew Porter, PhD, Imperial College London, U.K. The study was supported by grants from the National Institutes of Health, the Dutch Science Organization, the Gottlieb Daimler and Karl Benz Foundation and the National Science Council of Taiwan.


Story Source:

The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. Christa Buecker, Hsu-Hsin Chen, Jose Maria Polo, Laurence Daheron, Lei Bu, Tahsin Stefan Barakat, Patricia Okwieka, Andrew Porter, Joost Gribnau, Konrad Hochedlinger. A Murine ESC-like State Facilitates Transgenesis and Homologous Recombination in Human Pluripotent Stem Cells. Cell Stem Cell, 2010; 6 (6): 535 DOI: 10.1016/j.stem.2010.05.003

Cite This Page:

Massachusetts General Hospital. "New type of human stem cell may be easier to manipulate." ScienceDaily. ScienceDaily, 11 June 2010. <www.sciencedaily.com/releases/2010/06/100608182649.htm>.
Massachusetts General Hospital. (2010, June 11). New type of human stem cell may be easier to manipulate. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2010/06/100608182649.htm
Massachusetts General Hospital. "New type of human stem cell may be easier to manipulate." ScienceDaily. www.sciencedaily.com/releases/2010/06/100608182649.htm (accessed August 28, 2014).

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