Q&A: Stem Cell Revolution

Q&A: I have heard for several times in the last few years about some stem cell revolution. Apparently we no longer need to use embryonic stem cells anymore. I was wondering if you could explain this. Thanks, Jennifer


Hi Jennifer,

It sounds like they are referring to induced pluripotent stem (iPS) cells. It is rare that we see true breakthroughs in science where one paper can shock the world, but this discovery was one of them.

For the longest time, embryonic stem cells (ESCs) were considered the holy grail of stem cells. They are pluripotent stem cells because they give rise to all the cells in an adult being but not to the placenta or amniotic sac. Due to this ability, stem cell researchers dreamed of a future where one could take an embryonic stem cell and turn it into the appropriate cell type when needed: new β-cells if the pancreas failed, new neural stem cells upon paralysis or stroke, new cardiomyocytes after a heart attack. The implications were enormous. The problem was that we needed embryonic stem cells.

Embryonic stem cells are not without controversy, the first reason being that the process of harvesting the embryonic stem cells prevents the embryo from ever going to term. The other problem with embryonic stem cells is that they derive from another embryo that is not yourself, so even if the desired cells could be generated, one could still have transplantation issues where your immune system recognizes it as foreign and thus, attacks it.

And then, in 2006, Yamanaka's group made a big discovery. He could take a type of skin cell called the fibroblast and "re-program" them back into an embryonic stem cell state through some molecular magic. Let me repeat that once again. One can turn a skin cell into an embryonic stem cell. Somehow, four genes (Oct4, c-Myc, Sox2 and Klf4) could turn off the skin cell instructions and turn on the embryonic stem cell instruction.

This shocked the world. No one really believed it at first. For the longest time, scientists have always believed in the unidirectional flow of development; for instance, a fertilized egg begets ESCs, which begets ectodermal cells, which begets skin precurors, which begets fibroblasts. A fibroblasts never went back to become an ESC; it only went the other way. However, Yamanaka demonstrated cells were actually plastic. It has been replicated hundreds of times (I've turned a skin cell into an embryonic stem cell), and not only that, this molecular magic isn't specific to only creating ESCs. One can turn skin cells to neurons, to heart cells, and even to liver cells, by using a different cocktail of genes.

And so with one paper, the issues of harvesting embryos for their embryonic stem cells or that of tissue rejection are non-issues. Currently, scientists are assessing the safety of these cells and trying to understand how this reprogramming actually happens. But let us imagine a future where your liver is beginning to fail. You go to a clinic and the doctor takes a skin biopsy. Then, in a lab somewhere, those skin cells are turned into embryonic stem cells, grown into large numbers, and then changed once again to liver cells. After, they then replace your damaged liver cells with these newly made cells. This may seem like a sci-fi story but it is finally getting within reach.

Takahashi, K., and Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676. Paper