A breakthrough in stem cell research was announced last week in a paper in the journal Science where researchers from the University of Wisconsin -Madison in the US and other colleagues reported how they reprogrammed human skin cells to behave like embryonic stem cells.
The report is grabbing the headlines not just because of the remarkably simple elegance of the science, the fact that introducing four genes is all that is needed to “reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem cells”, but also because of the profound impact it appears to be having on the ethical debate surrounding stem cell research.
Leading bioethicists like R. Alta Charo, a UW-Madison professor of law and bioethics are saying that the discovery is starting to “redefine the political and ethical dynamics of the stem-cell debate”, and could neatly sidestep the ethical and legal problems surrounding use of embryonic stem cells, because, as Charo explained:
“This is a method for creating a stem cell line without ever having to work through, at any stage, an entity that is a viable embryo.”
The research was carried out in the lab of UW-Madison biologist and professor of anatomy at the University of Wisconsin School of Medicine and Public Health, James Thomson, the scientist who in 1998 was the first to recover embryonic stem cells from human embryos. This time the study was led by led by Junying Yu of the Genome Center of Wisconsin and the Wisconsin National Primate Research Center.
Speaking about this latest breakthrough, Thomson said:
“The induced cells do all the things embryonic stem cells do. It’s going to completely change the field.”
Embryonic stem cells are valued above all others because so far they are the only kind shown to be truly “pluripotent”, that is having the capacity to become any of the 220 types of cell in the human body. They have the potential to generate new heart, liver, brain, muscle and bone tissue, and replace diseased or damaged tissue in people who are ill with cardiovascular, Alzheimer’s, Parkinson’s and a whole range of the other diseases including diabetes.
Scientists at UW-Madison said that the new method developed by Yu and colleagues brings the generation of pluripotent stem cells within easy reach of many labs of “moderate sophistication”.
The other advantange of the new method is the fact that using cells drawn from the patient’s own skin, the stem cells can be customized to the patient, bringing numerous benfits, such as the elimination of immune system rejection.
Thomson put it like this:
“They are probably more clinically relevant than embryonic stem cells.”
In the new study, Yu, Thomson and colleagues introduced four genetic factors, OCT4, SOX2, NANOG, and LIN28, into human fibroblast skin cells that are easy to harvest and grow in culture.
Finding the set of genes that had the capacity to make the skin fibroblast transform into unidifferentiated stem cells helped overcome problems that exist ever since scientists created Dolly, the famous sheep that was cloned in the UK in 1996. Dolly was made by transferring an adult cell nucleus into an unfertilized egg.
This was the only way to generate embryonic stem cells “cloned” from the donor nucleus. An unknown process reprogrammed the adult nucleus in the oocyte (the egg) so that it had the capacity to make emrbyonic stem cells and then divide and reproduce once implanted in a surrogate mother ewe.
Yu, Thomson and colleagues have shed some light on the mysterious reprogramming process by introducing four gene factors inot skin fibroblasts that give them the same characteristics as embryonic stem cells, without having to go through the oocyte stage, and without using the cloning techniques like those that led to Dolly.
“These are embryonic stem cell-specific genes which we identified through a combinatorial screen.”
“Getting rid of the oocyte means that any lab with standard molecular biology can do reprogramming without difficulty to obtain oocytes,” he added.
The researchers managed to create eight new stem cell lines using the new method, some of which at time of writing the paper, had been growing continuously in culture for 22 weeks.
It is clear that it is still early days, and the breakthrough does not mean an end to embryonic stem cell research. For instance, many more comparison studies are needed to show that the new cells “do not differ from embryonic stem cells in a clinically significant or unexpected way,” cautioned Thomson.
“It is hardly time to discontinue embryonic stem cell research,” he added.
Thomson said more work was also needed to fine tune the methods, for instance to stop the introduced genes from disrupting the patient’s DNA and causing other diseases like cancer. Another area that has to be carefully developed is to ensure that the deactivated virus vectors used to carry the four genetic components are removed safely.
These are considerable challenges for researchers, so although they, like Thomson, are encouraged that the discovery will eventually lead to new cell-based therapies to treat disease, it will be some years before therapies can be developed and tested through the usual clinical trials.
“Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells.”
Junying Yu, Maxim A. Vodyanik, Kim Smuga-Otto, Jessica Antosiewicz-Bourget, Jennifer L Frane, Shulan Tian, Jeff Nie, Gudrun A. Jonsdottir, Victor Ruotti, Ron Stewart, Igor I. Slukvin, and James A. Thomson.
Science Published Online November 20, 2007
Written by: Catharine Paddock