The Niche

Stem cells, down to one factor

Differentiated human cells have been reprogrammed to an embryonic-like state with the addition of only one gene, rather than the standard four 1. This should advance techniques for the efficient production of high-quality patient-specific stem cells.

The ability to make induced pluripotent stem (iPS) cells using cells from specific patients could enable unprecedented new ways to study disease and also ease the development of cell therapies. However, such applications have been stymied in part because making induced pluripotent stem cells efficiently requires the introduction of pluripotency genes, which are typically inserted at random sites throughout the genome. This unwanted source of variation stymies rigorous comparisons between cells, and could make them behave in unpredictable, dangerous ways if used for cell therapies. Several techniques to make cells without permanent insertion of the genes have been reported, including some that do not use genetic material at all.

See: Human iPS cells with no genetic integration

Virus free pluripotency for human cells

Integration-free iPS cells

Reprogramming to pluripotency without genetic engineering

Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins

However, researchers are eager for additional, ‘gentler’ ways to reprogram cells, and one possibility would be starting with cells that are more prone to reprogramming. Evidence in mice suggests that the tissue of origin affects how often and how well differentiated cells reprogram.

See: Cell origin and variation in induced pluripotent stem cell lines

Stomach and liver cells reprogrammed

Scholer and colleagues reasoned that neural cells would be a good candidate, since these cells already express high levels of three of the four standard pluripotency factors (Sox2, Klf4 and c-myc). The team had previously shown that this strategy worked in mice. The researchers used viruses to insert copies of the fourth pluripotency factor, Oct4, into the cells. This produced reprogrammed cells that passed all standard tests of pluripotency.

The current study reprogrammed neural stem cells from human fetal tissue. While adult tissues tend to be more difficult to reprogram, and brain biopsies are difficult to obtain, Scholer and colleagues say they are already working out practical solutions. More-accessble cells, such as those found in dental pulp, might also be good candidates.

1. Kim, J.B. Direct reprogramming of human neural stem cells by OCT4. Nature advance online publication, doi:10.1038/nature08436 (28 August 2009)


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