A Stem Cell First: Using the ‘Dolly’ Method on Human Cells

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The New York Stem Cell Foundation

Immunostaining for pluripotency markers

Scientists from the New York Stem Cell Foundation Laboratory reported on Wednesday the first success in using the cloning technique that gave rise to Dolly the sheep to generate stem cells using adult human cells.

The advance brings the field of stem cell research closer to its ultimate goal: being able to treat conditions such as diabetes and spinal cord injury by replacing malfunctioning cells with healthy ones, made specially for each individual patient. The discovery also moves science closer to human cloning.

“Though not unexpected, it is nonetheless a landmark,” says Dr. George Daley, a leading stem-cell researcher and professor at Children’s Hospital Boston and Harvard Medical School, of the discovery.

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Researchers used a variation of a technique known as somatic cell nuclear transfer (SCNT), which has been studied extensively in animal cells. SCNT involves replacing the genetic material of an egg cell with the DNA from a mature cell (a skin cell, for example). The egg is then stimulated to divide, and if it develops fully, produces a genetically identical clone of the animal from which the mature cell was taken.

Dolly was the first animal to be cloned this way, in 1996. She was followed by cats, dogs, mice and a slew of other animals. However, cloning isn’t what the researchers were after in the new study. SCNT can also be used to generate valuable embryonic stem cells, the mother cells that can develop into any of the more than 200 cell types in the body. Any stem cells made from a donated adult skin cell would share the same DNA as the donor, and, therefore, if these healthy cells were to be used to replace the donor’s damaged cells, they would not risk immune rejection.

In theory, that’s how it should work. But scientists have been trying for more than a decade to coax human eggs and skin cells to merge in the right way to generate stem cells — without success. The genetically altered egg has always stopped progressing after a few rounds of cell division, leading frustrated researchers to wonder whether the human egg was even capable of creating stem cells in this way.

The field has also weathered controversy along the way: South Korean scientist Woo Suk Hwang claimed he had created human stem cells using SCNT in 2004, but it turned out his work was flawed.

MORE: First European Embryonic Stem Cell Trial Gets Green Light

Now, the New York-based researchers report in Nature that they have come very close to making SCNT work with human cells. They did not perfect the technique, however; rather than fully replacing the egg’s genetic material with that of another cell, they had to combine DNA from both cells to make the process work. The researchers created two lines of stem cells: one using skin cells from a healthy adult, and another using skin cells from a patient with Type 1 diabetes.

Since the resulting stem cells contained excess chromosomes, they are rendered therapeutically useless, but the discovery is critical — it shows that the human egg does indeed have the ability to reprogram a mature skin cell back to an embryonic state.

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