IPS Cells - Scientific Finding of the Year

The scientific finding of the year has to be the reprogramming of adult somatic cells into induced pluripotent stem cells (IPS cells). In reality the ground breaking work was published in 2006, however at that time it was not yet clear whether IPS cells were the real thing.

In 2007 IPS cells were indeed shown to be totipotent in the sense that an entire animal can be generated from IPS cells. It is true that for this to occur, IPS cells must be injected into a tetraploid blastocyst, but generally, IPS cells are functionally equivalent (in mouse) to embryonic stem cells. If you start looking at the details there are some differences. IPS cells are not 100% full proof - many injected embryos did not develop. Also there is the problem that the original protocol for generating IPS cells involves the incorporation of 2 proto-oncogenes, and as a result the cells have a high tendency to form teratomas, a form of cancer. However in the last few months this problem has been partially overcome through the modification of the IPS cell protocol so that no proto-oncogene has to be activated in order to reprogram the cells.

Why is this finding important?

First there is the obvious potential therapeutic benefit. In fact the Jaenisch lab has already used IPS cells to cure sickle cell anemia in a mouse model of the human disease. Now the biggest obstacle for therapeutics, is figuring out how to activate the four (or three) genes without the use of retroviruses. Since the IPS cell protocol involves the activation of 3-4 genes over weeks, this will be quite a hurtle to overcome (but not impossible).

Secondly IPS cells can become a useful tool in studying human disease. Want to figure out why amyloid plaques cause Alzheimer's? You could potentially take cells from an Alzheimer's patient, turn them into IPS cells and then differentiate these cells into neurons. Wow!

Third, and in my mind the most important implication of this work, is that the IPS cell protocol allows us to reprogram cells. It gives us insight into how cell fates are specified and how the genomic architecture specifies different phenotype. It also indicates that a cell's identity is quite malleable. Now if we were talking about amphibians, which can readily regrow amputated limbs, or flatworms, such as planaria, which can regrow any body part (including an amputated head), I would not be so surprised. In most organisms, the germ cell line, which includes the progenitors of sperm and oocyte cells are segregated from the rest of the organism at an early age. It is as if those cells were special and they had properties that have been illuminated from the rest of the body's cells. Why is that? And now that we know that there are cells in the body that can be reprogrammed - why don't we see this reprogramming in our bodies? (Excluding the "de novo creation of oocytes" controversy aside.)

Fourth, since we can create cells that can generate whole animals WITHOUT conception (and yes there is the implantation step) clearly the religious dogma that purports that a "soul" is created upon conception is false. Nature, it seems, does not view conception as anything special - only a way to swap genes on and off chromosomes. Conception is not required to stimulate the development. It is time that the right wing evangelicals reexamine their beliefs. Seriously. And I'm not the only one saying this.

Two further puzzles with the IPS protocol:

First, very few cells that undergo the protocol actually form IPS cells, and apparently the IPS cells vary quite a bit in their properties. It is unclear why this is. I suspect that it has to do with the fact that the cells that are being reprogrammed are the adult stem cells that exist in almost every tissue in our body. Those cells are half way there and it wouldn't be surprising if they were the ones easiest to nudge over.

Second, it takes a long time for cells to be converted to IPS cells. So maybe our notion that cells can be easily reprogrammed is false. What happens during this transformation is unclear. Clearly the reconfiguration of how the cell's genome is packaged may have something to do with it.

Here's a bunch of links to previous IPS cell entries:

Read this stem cell paper!
Yes it is true, you can now make your own stem cells
Induced stem cells, will they be useful for therapy?
Rudy Jaenisch on Stem Cells
Drinking with Cellular Alchemists
Stem Cell Discussion on the Diane Rehm Show
Some thoughts on the IPS cell findings - genes and the power to create "souls"
More thoughts on IPS Cells
Recent Events in Stem Cell Research