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YOUR BODY can be a source of embryoniclike stem cells. Also available is a special interactive, rich media version of this article. Image: BRYAN CHRISTIE DESIGN
- Induced pluripotent stem cells are mature body cells that have been made to change their identities and revert to an embryolike state—without the help of eggs or embryos.
- Rejuvenating the normal body cells of any individual—then converting them to any of the 220 human cell types—could yield new disease treatments and custom replacement tissues.
- Scientists are now working to understand how these cells are able to reverse their biological clocks and whether the newest kind of stem cell will prove as powerful as embryonic cells.
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I remember my excitement one morning in the winter of 2006 when I peered through a microscope in my laboratory and saw a colony of cells that looked just like embryonic stem cells. They were clustered in a little heap, after dividing in a petri dish for almost three weeks. And they were glowing with the same colorful fluorescent markers scientists take as one sign of an embryonic cell’s “pluripotency”—its ability to give rise to any type of tissue in an organism’s body. But the cells I was looking at did not come from any embryo: they were regular adult mouse cells that had seemingly been rejuvenated by the addition of a simple cocktail of genes.
Could it really be so easy to roll back the internal clock of any mammalian cell and return it to an embryonic state? I was not the only one wondering at the time. Shinya Yamanaka of the University of Kyoto and his colleagues had just published a groundbreaking study in August 2006 that revealed their formula for creating what they called induced pluripotent stem cells (iPSCs) from the skin cells of mice. Researchers had been struggling for years to understand and control the enormous potential of embryonic stem cells to produce customized tissues for use in medicine and research—as well as contending with political and ethical controversies over the use of embryos, scientific setbacks and false hopes generated by previous “breakthroughs” that did not pan out. So stem cell scientists were surprised and a little bit skeptical of the Japanese group’s results at first. But that morning in the lab, I could see firsthand the results of following Yamanaka’s recipe.
Other scientists were also able to reproduce his achievement, and improved techniques for making and testing iPSCs have come rapidly over the past few years. Today thousands of scientists worldwide are working to develop the potential of iPSCs to help in understanding and treating human diseases that have so far defied cures, such as type 1 diabetes, Alzheimer’s disease and Parkinson’s disease. The possibility of changing a cell’s identity just by delivering a few select genes has transformed the way scientists think about human development as well.
Throughout history people have dreamed of finding a Fountain of Youth to escape the consequences of aging and disease, and the ability to return an adult body cell to an embryonic state would certainly appear to be as close as humanity has come to that fantasy so far. Of course, the technology is still in its infancy. Many important questions must be answered before anyone can say whether iPSCs will change the practice of medicine or even whether they will actually prove equivalent to the more controversial embryonic stem cells.
To understand the hopes inspired by the discovery of iPSCs, one must return to what makes embryos so special. Current iPSC studies rely heavily on techniques and concepts developed in work with embryonic cells over the past 30 years, particularly the phenomenon of pluripotency. Mammalian development is normally a one way-street, where cells become progressively more specialized and less versatile with time, a process called differentiation. Only during a brief window very early in development do all the cells within an embryo possess the ability to become any of the 220 cell types in the human body. Extracting those cells and growing them in culture gives rise to embryonic stem cells. The ability of true embryonic stem cells to indefinitely maintain their capacity to generate any tissue type defines the term “pluripotent.”
Even in a late-stage embryo, stem cells have specialized to the extent that they can give rise only to specific families of cell types, such as those in muscle and bone. These cells are considered “multipotent,” but they are no longer pluripotent. In an adult, all that remains of those precursors are so-called adult stem cells that replenish mature cells within a tissue. Blood stem cells continuously regenerate the 12 different blood and immune cell types, for example, and skin stem cells are responsible for regrowing our skin and hair every few weeks.