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Human Stem-Cell Breakthrough

Adult human cells finally have been manipulated into becoming fully pluripotent human ESCs.

In late 2007, two laboratories reported breakthroughs that one day could make possible all of the potential benefits of human embryonic stem cells (ESCs) with none of the ethical objections. How did this come about? First, some context:

In 1997, the famous cloned sheep, Dolly, was created by nuclear transfer (Journal Watch Mar 14 1997): The nucleus of a differentiated adult cell was placed into an egg from which the nucleus had been extracted. Signals in the egg cytoplasm then "reprogrammed" the adult nucleus to return to an embryonic state. The embryo was placed in a ewe’s uterus and developed into Dolly. This same nuclear transfer technique was then used in various mammals to harvest ESCs from embryos. In 2005, a Korean team claimed (fraudulently) to have achieved the same feat in humans (Journal Watch Mar 9 2004). Even if the Korean team had succeeded, some would have regarded the feat as unethical, because it involved the creation and destruction of a human embryo.

In 2006, a Japanese team distinguished genes that are turned on in an embryonic stem cell from those activated in an adult cell and identified candidate genes that they hypothesized turned a cell into an ESC. In June 2007, the Japanese team, along with two American teams, reported that they had been able to trick fully differentiated mouse cells into becoming undifferentiated pluripotent cells with all the characteristics of mouse ESCs by introducing these genes (Journal Watch Jun 21 2007).

In November 2007, the Japanese team and another American team reported the same feat with human cells (Journal Watch Nov 29 2007). Both teams introduced four genes into differentiated cells using retroviral vectors. Cells, with all the properties of human ESCs, now can be made that contain the genome of a specific patient; such cells should not engender immune rejection. Moreover, such cells can be made without creating (and destroying) a human embryo — the primary ethical concern about ESC therapy. However, manipulated cells can become cancerous with the techniques used now, so more work is needed to optimize this approach. Finally, in December 2007, scientists used ESC-like cells that were made from mouse skin cells to cure sickle cell anemia in mice (Journal Watch Dec 13 2007). Because of all of these landmark studies, 2007 likely will be regarded as a turning point in the history of human stem-cell therapy.

— Anthony L. Komaroff, MD

Published in Journal Watch General Medicine December 28, 2007