A "breakthrough" in the field of stem cell research could mark “the beginning of a new era for stem cell biology, reported The Guardian today. Widespread media coverage was given to new research that has successfully reprogrammed ordinary skin cells to resemble and behave like embryonic stem cells. The Times reported that the new cells are “as versatile as those from human embryos, with the potential to form any kind of human tissue”.
Many of the newspapers report on the ethical implications of the research; that the ability to pre-programme ordinary cells could mean no further need to clone human embryos to create stem cells, with its attendant ethical controversy.
The newspapers also focus on the idea that the new technique could lead to developments in the treatment of conditions such as Parkinson’s disease, heart disease and diabetes, as the stem cells could be "grown to order" in a lab and then transplanted into a patient’s body without the rejection risks of conventional donor tissue.
The reports are on two separate studies that were carried out by teams of scientists in Japan and the US and published simultaneously in different journals.
Despite the implication in some of the reports that this research could mean the end of using cells from human embryos in research, many of the newspapers also quoted the researchers as saying that cells from embryos are still necessary. One of the authors, James Thomson, said that cells derived from human embryos “are the gold standard we need to compare against”.
It is also clear that much more research will be needed before this type of stem cell can be used to treat human disease.
The Japanese study involved Dr Kazutoshi Takahashi and colleagues from Kyoto University, the Japan Science and Technology Agency, and the Gladstone Institute of Cardiovascular Disease in San Francisco carried out this research. The study was funded by the Program for Promotion of Fundamental Studies in Health Sciences of NIBIO, a grant from the Leading Project of MEXT, a grant from Uehara Memorial Foundation, and Grants-in-Aid for Scientific Research of JSPS and MEXT. It was published in the peer-reviewed scientific journal, Cell .
The US study involved Dr Junying Yu and colleagues from The Genome Center of Wisconsin, University of Wisconsin-Madison, and the Cell Research Institute, Madison, USA, carried out this research. The study was funded by the Charlotte Geyer Foundation and the US National Institutes for Heath. One of the authors of the paper declared that he owns stock, serves on the Board of Directors, and serves as Chief Scientific Officer of Cellular Dynamics International and Stem Cell Products and as Scientific Director of the WiCell Research Institute. It was published in the peer-reviewed journal, Science .
Both studies were experimental studies investigating whether human skin cells could be converted into stem cells (cells that have the potential to develop into any of the different cell types of the body).
In the Japanese study, the researchers took skin cells from the face of a 36-year-old adult male, and grew them in the laboratory. They then infected the cells with viruses containing genes encoding four different human proteins (Oct3/4, Sox2, Klf4, and c-Myc). The viruses were of a type called retroviruses that can insert their DNA (the so-called blueprint of life) into the DNA of the cell they infect.
The researchers then monitored the infected cells to see whether the viruses would cause the cells to change their shape and size to look like stem cells that would be produced from human embryos.
Any cells that looked like stem cells were isolated, grown separately, and their behaviour observed. The researchers were interested in seeing if the cells were expressing genes and producing proteins typically expressed by human stem cells. They also assessed whether the cells grew and divided in a similar way to human embryonic stem cells.
To see if the cells would then develop into different cell types, the researchers grew the cells and examined them to see if they were changing in shape to resemble the appropriate cell. They were then tested to see if the genes that were "turned on" (expressed) were typical of the types of cells that they now resembled.
In addition, the researchers injected the cells under the skin of mice to see what sort of tissue developed.
They repeated these experiments using cells taken from the joints of a 69-year-old male.
The US study had a similar approach. The researchers also used genes inserted using a retrovirus to investigate whether the cells would resemble stem cells. This team used foetal and newborn skin cells to develop the technique and a slightly different set of genes within the retrovirus.
The Japanese study showed that after 25 days of being infected with the retroviruses, some of the cells began to resemble human embryonic stem cells. When these cells were isolated, they were found to be expressing many of the genes typically expressed by human stem cells, although some of these genes were more or less active than those in embryonic stem cells. Some of these genes had not been active in the original skin cells.
The cells divided at a rate similar to human embryonic stem cells. When grown in conditions that supported their development into embryonic cell types, they started to change shape, and express genes typical of the three main types of cells found in human embryos, which later develop into all of the tissues of the body.
The researchers also found that the cells could develop to a state where they resembled and expressed genes similar to nerve tissue cells, or heart muscle cells. When injected under the skin of mice, the cells went on to form tissue that resembled human stomach tissue, muscle tissue, cartilage, nervous system tissue, fat tissue, and skin tissue. The researchers also found that they could get similar results using cells taken from adult joints.
In the US study, the researchers found that the first combination of 14 genes that they added to the human cells caused the cells to take on some of the characteristics of human stem cells, in terms of shape, expression of typical proteins on the surface of the cells, and ability to form tissues resembling normal human tissues when injected into mice. When they looked at subsets of these 14 genes, they found that they could induce similar changes using a subset of only four of these genes (OCT4, SOX2, NANOG , and LIN28 ). They found similar results when they used these four genes in human foetal skin cells.
Twelve days after infecting the skin cells with viruses carrying the four genes, they found that cells took on the appearance of stem cells. They appeared to have normal chromosome structure under the microscope, and expressed genes in a way more similar to that of human stem cells grown in the laboratory than original foetal stem cells. They found that cells with the four genes could develop into the three main types of cells found in human embryos, and into tissues resembling normal human tissues when injected into mice. They found similar results when they used skin cells from newborns.
The Japanese researchers concluded that it is possible to create human stem cells from fully developed adult cells, and that these stem cells are capable of differentiating into different types of human cells and tissues. They say that their study “has opened an avenue to generate patient and disease-specific pluripotent stem cells” and that further studies are needed to see if these cells can replace human embryonic stem cells for use in medical applications.
The US researchers concluded that they have created cells similar to stem cells from foetal and newborn skin cells, and that these cells, like embryonic stem cells, “should prove useful for studying the development and function of human tissues, for discovering and testing new drugs, and for transplantation medicine.”
This research heralds a potentially exciting area of new research for scientists. It also provides a possible solution to both ethical and practical difficulties that have ensnared the field of stem cell research.
If functional stem cells can be generated from the skin, and need not be harvested from embryos, this should avoid many of the ethical concerns that people have about the generation of human embryos for scientific research. Also, creating stem cells from skin cells, a much more abundant and available source than embryonic cells, could speed up research for new therapies.
Of equal scientific and general interest, is the potential for stem cells that could be generated using ordinary cells from any adult, creating cells, tissue or even organs that are grown for a specific purpose for an individual. Anything grown from these cells would then also have less chance of being rejected when reintroduced into the individual’s body than that which originated from a donor.
It is probable that much more research will follow on from this development; however, it will be some time before this type of stem cell could be used to treat human diseases. In particular, because the technique uses retroviruses to insert specific genes into the DNA of the cells, scientists will have to ensure that this does not make these cells unsafe for use in patients. Also, although these cells are similar to human embryonic stem cells in terms of the genes the express, they are not identical, and these differences may limit their usage in as yet unforeseen ways.