The process is called reprogramming and had only been achieved previously by introducing genes into skin cells; the latest research, emerging from a researchers at the Karolinska Institutet, the University of Helsinki and King’s College London, used CRISPRa to directly activate genes within skin cells.
Unlike in other uses of CRISPR technology, the method does not involve cutting the DNA but is instead used to active gene expression – potentially making it a safer method of producing stable stem cells.
Timo Otonkoski, a main author of the study, explained to us why this is: “The traditional methods of reprogramming are based on numerous random and stochastic events in the cells that start to express the transgenes at variable levels. This often results in partial or aberrant reprogramming and may also result in ‘cancer-like’ genetic changes.”
He explained the difference in his current research, “With our method, the process is more controlled because it is based on the activation of the cell’s own genes instead of transgenes and also the expression levels of the genes are more moderate. At least theoretically, this should result in a more reliable and consistent outcome. Even if our method is not (yet) very efficient, it appears that the stem cells that come out of this process resemble more closely the embryonic stem cells than iPS cells produced with traditional methods.”
The potential of stem cells
The question of how best to produce stem cells is a pressing one for researchers, and has led to a number of alternative routes to the end goal – such as by using seaweed. It is hoped that stem cells could provide various uses therapeutically, with the potential to test the efficacy of drugs being one possibility.
Otonkoski noted where he sees potential for stem cells and how his research factors in: “Pluripotent stem cells can give rise to any type of cell in the body. Therefore, the potential for regenerative therapies is huge. The first examples of such therapies are emerging (e.g. retinal cells, heart cells, certain types of ion neurons, pancreatic beta cells). We hope that the CRISPRa reprogramming will help in making these therapies safer in the future.”
He also revealed that the reprogramming being done in the research could be scaled up to meet potential demand, though the real issue lies in the “expansion of the stem cells in high-volume cultures”.
The next stage for research is to improve its efficiency and to be able to skip reprogramming to the pluripotent stage, in order to convert cells directly to new types – with Otonkoski giving the example of turning fibroblasts to neurons.