Creating Stem Cells from Skin Cells: Promise, Limitations and Implications for Parkinson's Disease Research
On Tuesday, November 20, news media around the world reported that two research teams, led by Shinya Yamanaka at Kyoto University in Japan and James Thomson at the University of Wisconsin, working with human adult skin cells, had generated cells with many of the physical, growth and genetic features typically found in embryonic stem cells. Known as "induced pluripotent stem cells" or iPS cells, these new cells can differentiate to produce other tissue types, including what appear at first glance to be cells similar to dopamine neurons (the cells of interest to Parkinson's scientists). While a great deal more research is required, iPS cells are generating excitement in the scientific community because of their potential to achieve the same goals as human embryonic stem cells and therapeutic cloning but without engendering political or ethical controversy.
To gain a fuller understanding of the capabilities and potential limitations of iPS cells, as well as their possible use in the development of new Parkinson's treatments, MJFF spoke to Ole Isacson, MD, Dr Med Sci. Dr. Isacson is professor of neurology and neuroscience at Harvard Medical School and a member of the Foundation's Scientific Advisory Board.
MJFF: Give us an overview of what the researchers have done.
Ole Isacson: Essentially, we know which genes are expressed in mouse and human embryonic stem cells. Drs. Yamanaka and Thomson have demonstrated that if you express a combination of four genes related to stem cells in an adult human skin cell, the adult cell will revert to a state where it can become any kind of cell in the body. It's a way to "reprogram" the cell to become more like an embryonic stem cell, if you will. Although Dr. Yamanaka's group and others have already showed that this could work in mouse cells, this is the first time it has been shown to work in a human skin cell. It is big-time news.
MJFF: Is this similar to therapeutic cloning?
OI: Yes and no. Therapeutic cloning (or somatic cell nuclear transfer) involves taking the genetic material from an adult cell, such as a skin cell, and putting it into an egg cell that has had its own genetic material removed. By coaxing this egg cell to start developing into an early-stage embryo, you can isolate embryonic stem cells that are genetically identical to the person who donated the original skin cell. The iPS cells are generated differently. You start with an adult skin cell as before, but now you simply "reprogram" that cell to become an embryonic stem cell.
MJFF: Are there differences between iPS and human embryonic stem cells?
OI: Yes, there are. It is not yet clear how critical such differences (however small) may be in using iPS stem cells in the future. The iPS cells generated by the researchers are pluripotent, meaning that, like embryonic stem cells, they can differentiate into any other cell type. So they clearly share most of the qualities of embryonic stem cells. But there are some gene expression differences, as well, which are detailed in the papers published today. More research is required to understand the implications of these differences on the therapeutic potential of these cells, whether using them for transplantation purposes or as a research tool for testing drugs in the lab.
MJFF: Will iPS cells "replace" human embryonic stem cell research?
OI: At this time, embryonic stem cells remain the "gold standard" for understanding how a cell develops and, in particular, how they convert into other cell types. No doubt the iPS finding is exciting, but iPS cells are still somewhat "artificial" because they have been engineered at the most basic level to look like embryonic stem cells; we don't know exactly what these cells are -- and more importantly, what they may or may not do. Whether they will completely mimic true embryonic stem cells, we just don't know yet.
MJFF: Where does that leave patients in terms of a timeline to better treatments and cures? Will iPS cells speed up drug development and cell replacement?
OI: My belief is that this finding is going to activate and energize the entire field of regenerative medicine, and this will have the effect of speeding things up. Now researchers in every disease field can potentially do many experiments without always hitting the stumbling block of needing to obtain stem cells from human embryos or egg donors. In addition, we are going to be able to transfer some of our understanding from past experiments using embryonic stem cells to iPS cells, meaning that with iPS cells, we are starting at a somewhat more advanced point. So in summary, this discovery enhances many different kinds of work, and that helps the entire field move forward with more momentum.
MJFF: Dr. Yamanaka and colleagues report that the iPS cells are capable of differentiating into dopaminergic neurons. What should people with PD take away from this?
OI: This is very encouraging news for those of us working in Parkinson's, but it's also important to remember that this finding is subject to all of the same research challenges that we have seen when working with embryonic stem cells to generate dopamine neurons. That is, how do you generate robust quantities of cells that look and act as much like authentic dopamine neurons as possible? How do you get them where they need to be in the brain? And how do you ensure that they will not only do everything you want, but not do what you don't want -- i.e., cause unwanted cell growth and tumors?
MJFF: What's the bottom-line takeaway?
OI: This basic discovery is a very important, exciting and unexpected finding. While a lot more work is needed to fully understand the implications of this work for people living with disease, it is clear that the paper will have a huge impact on the entire field of regenerative medicine. It also worth mentioning that this is an excellent example of the potential of basic biological research on stem cells to open up entirely new, surprising and useful medical research avenues. As such, it is an argument in itself for continued and expanded stem cell research.