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Human Skin Cells Turned Into Stem Cells
Jason West, Shannon McKinney-Freeman, Ph.D., Susan Garfinkel, Ph.D., and Suzanne Kadereit, Ph.D.

In the August 2005, issue of the journal Science, Kevin Eggan and colleagues at Harvard University fused human skin cells and human embryonic stem cells. The resulting hybrid cells retained properties of the embryonic stem cells, suggesting that specialized adult cells can convert into a less specialized state.

Prior to this study, the ability to coax a more specialized adult cell (or the DNA of an adult cell) into a less specialized state had been demonstrated via the process of somatic cell nuclear transfer. In that process, an adult cell is fused with an egg, whose own genetic material is removed, so the egg contains the genetic material from the adult cell. The egg is then coaxed to develop like a fertilized egg, and at the blastocyst stage of development (about 4-5 days and 100-200 cells), embryonic stem cells can be isolated that are a genetic match to the adult cell donor. This procedure has generated much controversy due to its use of unfertilized human eggs (which must be donated) and the creation, and subsequent destruction, of human embryos to enable the isolation of embryonic stem cells.

The current study directly fused adult skin cells with existing human embryonic stem cells, so no human eggs were involved. Although the fused cells still contained the genetic material, or DNA, from both of the two cells used (adult skin cells and embryonic stem cells), they behaved very much like embryonic stem cells. The fused cells could generate many different cell types of the body, including brain cells, hair cells, skeletal muscle and intestine and also expressed many genes that are characteristic of embryonic stem cells.

It remains to be determined if the fused cells, which contain twice the amount of DNA as a normal cell, will form functional cells that will be useful for treatments. Even embryonic stem cells derived in the classical way (from human eggs at the blastocyst stage) have yet to be used successfully to treat human disease. Thus, many challenges still remain in simply characterizing these exciting new cells and understanding the extent to which they mirror embryonic stem cells. Clinical uses are undoubtedly years down the line, if at all.

However, despite these limitations, this research offers an exciting hope that someday any adult cell could be converted into an embryonic stem cell. Normally, a cell is guided through development from a less specialized state to more specialized state by a specific program. Although cells share common DNA, specific factors within cells influence the DNA, allowing one cell type to be distinguished from another. For example, a nerve cell and a heart cell within a person have the same DNA, but other factors program the nerve cell to be a nerve cell and the heart cell to be a heart cell.Thus, changing these factors will change, or reprogram, one cell into behaving like a different cell.

This research showed that factors present within the embryonic stem cells, instead of human eggs, caused adult cells to reprogram. Future studies aimed at identifying what factors are responsible will likely grow out of this research. In addition, the reprogramming of adult cells by embryonic stem cells, in lieu of human eggs, has overcome the hurdle of getting enough raw materials to study the factors causing reprogramming, since human eggs are a scarce commodity and embryonic stem cells are available in vast numbers. Nonetheless, the current procedure still required the use of embryonic stem cells that were created from human embryos, and therefore still raises controversy among some groups opposed to research using embryonic stem cells.

In the future, knowledge of factors necessary for reprogramming could potentially allow for the creation of “embryonic” stem cells arising directly from an adult cell without the use of any preexisting embryonic stem cells or human eggs. It must be noted, however, that years of research on other model systems such as the frog and mice have failed to identify such factors that allow for successful reprogramming of an adult cell without the use of eggs or embryonic cells. Thus, this procedure currently only allows for the generation of fused cells with twice the genetic content of normal human cells and does not offer an alternative to using human embryonic stem cells. Even so, it offers an exciting new tool to study reprogramming for stem cell researchers.