From skin cells to stem cells?

Stem cells are unspecialised cells that can develop to form almost all cell types in your body – just like Mystique in X-men. Similar to the movies, this ‘shapeshifting’ ability makes these types of cells extremely valuable in medicine. From generating new skin for burn victims, to creating new organs in the lab, these cells undoubtedly have the potential to improve our quality of life.

Nevertheless, these highly unspecialised pluripotent embryonic stem cells (ESC) only reside in rare places within the body, including developing embryos. As they are obtained from embryos, this has raised a number of ethical issues. Thereby, a new method of reprogramming specialised adult cells has been developed: induced pluripotent stem cells (iPSC).

Imagine an egg. It has the potential to become a lot of things if you add the right ingredients. For instance, you can make a delicious Victorian sponge, or you can make a piping hot omelette. The Nobel-prize-worthy question is: can you turn the final product back to its original ingredient? Put the egg back into its shell?

This answer is yes! iPSCs are essentially the product of reverting the cake or an omelette back into its raw, untouched form; a Japanese scientist, Shinya Yamanaka, successfully developed this reprogramming technology back in 2006. However, this process is extremely difficult, and the efficiency of the reprogramming process is less than 1%. To put this into context, according to Amram Shapiro’s book The Book of Odds, there is a higher chance of getting into Harvard than successfully turning a specialised cell into an iPSC.

“From new organs to regenerating skin, stem cells can undoubtingly improve our quality of life”

Such low efficiency hinders the transferal of this technology into the clinic, so constant efforts are being made to improve the process. Recently, a group led by Ganna Bilousova, Ph.D. in the University of Colorado Anschutz Medical Campus, US, has uncovered a more efficient way to create iPSCs from skin cells.

By introducing a cocktail of molecules that control how genes turn on and off (modified nucleobases, supplemented with ESC-specific mature micro-RNA mimics), the group has successfully enhanced the efficiency of the reprogramming process.

Not only did they create this unique mixture of molecules, but they also optimised the way these molecules are introduced into the skin cells. This means that the adult cells are more receptive to the changes, and less likely to die from the reprogramming process. Additionally, the cell growing regime was fine-tuned by having a low plating density, thus cells are less crowded and grow faster. These changes allow a maximum efficiency for turning skin cells into iPSCs.

By augmenting both the culturing conditions and the level of reprogramming molecules, these modifications acted synergistically to improve the process. Upon inspection, the results of the gene expression profile hinted that other players, such as SLLA4, may be mediating the process of reprogramming.

Altogether, this allows an ultra-high efficient system where both diseased and healthy skin cells can be turned into iPSCs in a cheaper, faster, and more reliable manner. Nonetheless, this protocol is cell-type specific, meaning more work is needed if we want to use this technique in the clinic or for treating other diseases. So keep eating your greens and head to the gym – growing organs in the lab is not quite here yet!