Monday March 2 2009
The Guardian has reported on a new way to “make an almost limitless supply of stem cells that could safely be used in patients while avoiding the ethical dilemma of destroying embryos”. The newspaper said scientists have found a way to reprogramme skin cells from adults, effectively reverting them to their embryonic form.
In 2007, researchers managed to create pluripotent (stem) cells from adult skin cells by using modified viruses to deliver new genetic instructions to the cells. However, this method cannot be used safely in humans as the viruses can also potentially affect normal cell function. This new research describes a virus-free method of transforming human cells into those that could potentially become any kind of specialised cell.
This is encouraging, yet early, research. Importantly, the cells that were converted to stem-cell-like cells were not originally human adult skin cells, but came from human embryonic fibroblasts (a type of connective tissue cell from embryos). Although adult mouse cells were used in one study, it still needs to be shown that the technique works in human adult skin cells.
Where did the story come from?
The news stories are based on the work of two teams which carried out a series of experiments that are published as two letters in the Nature journal. The teams were led by Dr Keisuke Kaji from the Medical Research Council (MRC) Centre for Regenerative Medicine at the University of Edinburgh and Dr Knut Woltjen from Mount Sinai Hospital in Toronto and Dr Andras Nagy from the University of Toronto.
The study was supported by grants from the Wellcome Trust, the Canadian Stem Cell Network and Juvenile Diabetes Research Foundation to some of the researchers.
What kind of scientific study was this?
Stem cells are cells that have the capacity to develop into any type of cell in the body. They are the subject of much research because of their potential application in treating disease. At present, one of the few known ways of sourcing human stem cells is from human embryos, which is controversial. In these laboratory studies, the researchers explored ways of delivering gene sequences into skin cells that would reprogramme them from being normal cells into pluripotent (stem) cells.
To change a differentiated cell (a cell that has already been specialised for a particular function, such as a skin cell) into one that has the potential to differentiate into any type of cell, only four transcription factors (proteins that control the switching on of specific genes) need to be activated in the cell. To date, the only way of achieving this in human cells was by using modified viruses to insert the genes for these transcription factors. However, as the viruses can also affect the normal function of genes, this method may be unsafe for transplanting the stem cells into actual patients. This research investigated a new method for reprogramming embryonic fibroblast cells (from humans and mice). Fibroblasts are connective tissue cells that are common in the skin.
The new delivery system used a method called the piggyBac transposon (a mobile sequence of DNA), which is an alternative way of carrying particular gene sequences into the DNA of a host cell. In this research, the researchers investigated how this system might be used to carry the genes that encode the four transcription factors necessary to induce pluripotency in human skin cells.
The researchers created a transposon carrying the four transcriptional factors, and introduced it into embryonic and adult mouse skin cells, and human embryonic skin cells. The researchers also introduced DNA carrying the code for an enzyme (called transposase), which can cut out the newly introduced piece of DNA (transposon) from the host when it has finished expressing the transcription factors. The researchers looked at whether the skin cells began to switch on genes that are typically expressed in pluripotent embryonic stem cells and began to look like embryonic stem cells.
In the experiments with embryonic mouse skin cells, the researchers also took the successfully reprogrammed cells and injected them into mouse embryos to see if they would successfully form different types of cell within the mouse embryo, that is, whether they were truly pluripotent.
What were the results of the study?
The two studies have similar results in that they have shown that a method of reprogramming cells that does not rely on the use of a viral vector can be applied to fibroblasts from embryonic and adult mice, as well as human embryonic fibroblasts. The reprogrammed cells stopped behaving like fibroblasts and took on the characteristics of pluripotent embryonic stem cells in terms of appearance and switching on of genes typical of embryonic stem cells. When injected into mouse embryos the reprogrammed cells showed properties of pluripotency (the potential to develop into any specialised body cell).
What interpretations did the researchers draw from these results?
The researchers conclude that their method of reprogramming cells is simpler and safer and has a wider range of application than methods that rely on potentially harmful viruses. Also, because the technique starts with cells from the host, the possibility of reactions to ‘foreign’ material may be diminished. Importantly, the system allows removal of the newly introduced genes from the host cells once the cells have been reprogrammed into pluripotent cells.
What does the NHS Knowledge Service make of this study?
This research is of interest to the scientific and medical community because it has demonstrated the successful application of a new method to reprogramme mouse and human cells. The approach uses a non-viral method of inserting new genes into host cell DNA and in these two studies achieved this in human embryonic fibroblasts (connective tissue cells). The news reports focus on the ethical issues involved with using embryos to source stem cells and how this may be avoided in the future if this method can be used with adult skin cells.
The study builds on previous research that used a virus to carry DNA into human skin cells to make them pluripotent. That approach was risky because of the potential negative effects of introducing viruses into human cells. This approach is considered less risky in that it uses a non-viral method to carry genes into the cells to reprogramme them.
One important point to raise in light of the way these studies have been interpreted by the newspapers is the fact that the research used fibroblast cells derived from human embryos, and not adult human skin cells. It remains to be seen whether adult human skin cells can be made pluripotent using this method. Much further research will also be needed to study the properties of these reprogrammed cells and their capabilities before they could potentially be used to treat human diseases.