The Nobel Prize in physiology and Medicine was awarded to Japanese doctor Shinya Yamanaka in 2012 for his work in the field of genetics. Yamanaka’s research group used high concept science – engineered viruses that injected DNA regulating molecules into cells – to force adult cells to revert to immature stem cells. Unfortunately, Yamanaka’s stem cells weren’t exactly medical grade, displaying a nasty predilection for developing into tumors instead of tissues. Two late January papers published by a Japanese-American research group in “Nature” outlined a new low-tech stem cell technique which promises to be both cheaper and safer.
In the world of stem cells, not all are created equal. “There are basically three types of stem cells” explained University of Wyoming cell biology professor Dr. Stephen Ford.
“There are totipotent stem cells – and those are cells that will develop into an entire conceptus – in other words will develop into the fetus and the placenta. All types of tissues. Then they have pluripotent cells which will develop into a variety of different tissues: all the tissues in the fetus except for the placenta. And then the last one is multipotent stem cells, and those will develop into a specific type of tissue or maybe a couple of different types of tissue.”
Of the three types, pluripotent have the widest range of applications in medicine. Pluripotent cells can be thought of as immature cells which have yet to choose a career. They are undifferentiated, which means that they have not yet started to switch genes off and on to specialize into a given role – say as a muscle cell or skin cell. In theory, pluripotent cells can be used to close wounds, heal damaged cardiac muscle, and even regenerate whole limbs or organs.
Pluripotent cells are functionally the same cell type as the much-debated embryonic stem cells. Yamanaka’s research proved the efficacy of taking differentiated adult cells and reverting them to the pluripotent state, dodging the controversy associated with harvesting embryonic cells. However, Yamanaka’s genetic manipulations led to other, less desirable cellular changes.
“He had four genes that he could insert into cells and actually get that cell to revert back to a pluripotent cell. Unfortunately, with that technology a lot of times you use viruses to insert those into cells, and those viruses can actually turn on cancer development” said Ford.
“Scientists already know how to de-differentiate cells” Ford continued. “Now they’re just looking for a way to do it so that when you put these cells back in they don’t cause cancer”
The procedure outlined in the two “Nature” papers is almost laughably simple compared to Yamanka’s cutting edge viral technique. The study simply soaked differentiated, adult blood cells from mice in a weakly acidic solution for twenty minutes. Many of the cells died, but a few survived. Of the survivors, approximately thirty percent were found to have reverted to a pluripotent state.
While this technique has obvious advantages in terms of simplicity and cost, it also potentially holds the answer to the question of tumor development.
“In these cells you’re not actually changing the [genes]. You haven’t inserted anything foreign into it” said Ford. This lack of direct genetic manipulation cuts the risk of cancer significantly, and while it may seem bizarre that a simple acid could achieve such results, the emerging science of epigenetics could provide the explanation.
“This is called epigenetics” said Ford. “It’s a new field of study which looks at how the environment will actually change gene expression.”
A differentiated cell has made the decision as to what its role in the body is going to be. If it is a muscle cell, this means that the cell needs to have access to all the genes related to its duties as a muscle, but doesn’t need any of the genes related to being a bone cell. All of the “bone cell” genes need to be turned off. This is accomplished in a number of ways, but one of the more common is by a chemical process called methylation. The Japanese-American group believes that their acid treatment may reverse the methylation, a case of epigenetic-affected cellular change.
“They suggest here that when they dip the cells in acid, that many of those methylated genes are no longer methylated” said Ford. ”They open up the entire genome. And so basically you’ve returned the cell to a state where it can read all of its genes.”
A cell which can access its entire genome is then capable of becoming any type of cell: it has become pluripotent. Furthermore, the cancer bullet is dodged as there has been no change to the sequence of the DNA, nor have any DNA regulating molecules been modified. If the results reported in “Nature” are replicable, stem cell treatments and technologies will have taken a major leap.
As Dr. Ford succinctly puts it, “this technology will just skyrocket.”
