BioBasics: Induced Pluripotent Stem Cells - Part 1


This fall, scientists announced two breakthroughs in stem cell research, and I’d like to tell you about one of them.

First, a quick review of stem cells. Stem cells are like “blank” cells, in that they haven’t differentiated into a specific type of cell, such as fat, blood, or skin. Stem cells that can turn into any kind of tissue, including the placenta, are totipotent—“all powerful.” A zygote is totipotent, because it has not differentiated into cells that become the placenta, and other cells that become an embryo. Embryonic stem cells are pluripotent—“many powerful.” These can turn into any tissue in the body.

Researchers are interested in pluripotent stem cells for their potential to repair all types of diseased or injured tissue. Embryos are the perfect source of pluripotent stem cells. That is, until you realize that the embryo must be destroyed to extract those stem cells.

Researchers have found an ethical way to create pluripotent stem cells. We have stem cells throughout our body, called adult stem cells that have already differentiated into a specific type of tissue. In 2007, Dr. Shinya Yamanaka found a way to revert these adult stem cells into pluripotent stem cells, essentially “turning back the clock.” His technique for creating induced pluripotent stem cells (“iPSCs”) triggered a wave of research.

The complex technique involves inserting four genes (called the “Yamanaka genes”) into the cell using a retrovirus. The technique for iPSCs isn’t perfect: the success rate is less than 1%. The cells don’t revert at the same rate, leaving the scientist with a mixed batch of cells. And, the retrovirus can increase the risk of cancer and the iPSCs can also form tumors.

Now for the breakthrough that solves the efficiency problem: A researcher in Israel found a way to reprogram adult stem cells into pluripotent stem cells with a success rate of almost 100%.[1] In addition to adding the four Yamanaka genes, the researchers turned off another gene, Mbd3.  This gene tells the cell not to be pluripotent. Dr. Jacob Hanna describes the effect of Mbd3: It’s like “trying to drive a car while stepping on the gas and brakes at the same time. The car can succeed, but it’s not optimal.”[2] By turning off the Mbd3 gene—like disconnecting the “brakes”—they reactivated the cell’s pluripotency. The good news is that all cells changed at the same rate—no more “mixed batches.”

This breakthrough in efficiency can open up more areas of research in regenerative medicine. We don’t know yet if this method will reduce or eliminate the risk of tumors and cancers. And, I have to caution you that unethical researchers might be able to make eggs and sperm out of these cells in order to create an embryo.

In the meantime, scientists have “taken off the brakes” in this amazing area of research that doesn’t require the destruction of human embryos. Next time, I’ll tell you about the other breakthrough. And that’s your science lesson for today.

[1] Ed Yong, “Inducing Pluripotency Every Time,” The Scientist, September 18, 2013, (accessed October 23, 2013

[2] Ibid.


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