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Older May Not Be Better

MedMag-Spring2012OLDER, ESTABLISHED HUMAN-EMBRYONIC-STEM-CELL LINES, including those approved for federal research funding under former President George W. Bush, differ from newly derived human-embryonic-stem-cell lines, according to a study by UCLA stem-cell researchers.

The finding, by scientists with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and published in the online edition of Human Molecular Genetics, highlights the importance of continuing to derive new stem-cell lines, so that researchers can better understand the ability of these cells to make every cell in the human body, says Amander Clark, Ph.D., assistant professor of molecular, cell and developmental biology.
The study looked at the first six new human-embryonic-stem-cell lines Dr. Clark's research team developed at UCLA from 2009 to 2011. These lines have been accepted by the National Institutes of Health's embryonic-stem-cell registry; acceptance into the registry allows the UCLA lines to be used in federally funded research projects.

In the study, Dr. Clark examined X-chromosome inactivation, a process by which normal female cells shut off one of their two X chromosomes during embryonic development. Dr. Clark wanted to compare this specific molecular signature in the established embryonic-stem-cell lines with what occurs when new embryonic-stem-cell lines are derived from human blastocysts.

In examining older lines derived prior to 2001, Dr. Clark found that with the progression of time, the molecular signature in these lines no longer reflected the normal process of X-chromosome inactivation. "The classic signature is gone, so something else is regulating X-chromosome inactivation in the established cell lines," Dr. Clark says. 

The new cell lines generated by Dr. Clark's research team were derived from human embryos donated by couples who had previously undergone in-vitro fertilization. Several weeks after culturing cells from the embryos, Dr. Clark's lab examined the new human-embryonic-stem-cell lines and found that both X chromosomes were still active in many cells, making them more like the original cells from which they were derived and less like the cells from the established stem-cell lines. Slowly, however, with time in a culture and cryo-preservation, one X chromosome is inactivated, and the cell lines become identical to the older, established lines, Dr. Clark says.

The question is, are the first cells to grow out from the original culture of a higher quality and therefore the ones researchers should be aspiring to use for research and potential therapies?


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