New Method Of Producing Pluripotent Stem Cells Makes Fewer, But Better Cells

Hebrew University. Artist's conception of one of the stem cells produced using a new mix of genes.

A new way to produce pluripotent stems cells has been shown to be more reliable at making cells suitable for clinical use.

Advances in stem cell science are appearing with great frequency. However, most of these rely on a the production of pluripotent stem cells, which can differentiate into any of the body’s cells.

Embryos represent one source, but much opposition remains to the use of embryonic stem cells. Numerous techniques have been developed to induce plurioptency in stem cells taken from adult bodies. However, there are levels of pluripotency, and many of these methods either fail to reach the highest grade, or do so with low reliability. Worse still, many of these cells show signs of genetic abnormalities.

Consequently, the announcement in Cell Stem Cell of an 80% success rate for producing maximally pluripotent mouse stem cells marks an important advance in the quest to replace damaged organs and treat diseases.

Induced pluripotent stem cells (iPSCs) are made by taking adult cells, preferably from the person in need of treatment, and injecting viruses that carry genes active in embryos. Different genes can be used, but the most popular are Oct4, Sox2, Klf4, and Myc. These genes won their discoverers a 2012 Nobel Prize.

By increasing the amounts of some of the four standard genes, and decreasing others, researchers have been able to improve the pluripotency of the stem cells. Adding chemicals such as Vitamin C has the same effect, but lead author Dr. Yosef Buganim of Hebrew University wanted to go further. He experimented with a new set of reprogramming factors, Sall4, Nanog, Esrrb, and Lin28, which his team collectively called SNEL.

Buganim found that SNEL produced just 1-5 iPSC colonies per 105 cells to which it was applied. This is much lower quantities than the old method, but eight out of the ten colonies tested passed the most stringent tests for pluripotency. His theory is that the Oct4 and Sox2 gene regulators cause some cells to begin activating genes for adult cells, limiting the potential cell types into which they can transform, while Myc may be responsible for many of the abnormalities.

The SNEL cocktail may not be suitable for use on human cells, but Buganim believes the same bioinformatics techniques that led his team to try these four factors could help identify a combination with similar potential when applied to us.

Buganim et al. The SNEL cocktail of genes produces far fewer stem cells, but of greater suitability for clinical use.

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