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Biomedicine

Cloned Human Stem Cells, with a Twist

Researchers create a genetic oddity in pursuit of a more versatile cell.

A team of New York City scientists has created human stem cells by implanting the nucleus of an adult skin cell into an egg cell—a feat otherwise known as cloning.

The advance represents a major success in human stem cell research. Researchers across the globe have been trying to clone human cells for at least a decade, because such cells have great potential value for both medical research and cell replacement therapies. But the procedure—which has become routine in other mammals—has proven extremely technically challenging.

“This work now demonstrates for the first time that the human egg has the ability to turn a specialized cell into a stem cell,” said lead researcher Dieter Egli in a telephone news conference on Tuesday. The research appears in today’s issue of the journal Nature.

In nuclear transfer, or cloning, the DNA of an adult cell is injected into an egg, which typically has its own DNA removed. The egg then develops into an embryo, from which embryonic stem cells can be extracted. (The need to create and destroy a human embryo has made the procedure highly controversial, and such research cannot be funded with federal grants.)

When Egli and collaborators tried the standard approach, the resulting cell would divide six or 10 times and then die. So instead, they left the egg’s DNA intact. The resulting cells have three sets of chromosomes—two from the cell donor and one from the egg. That makes the cells unsuitable for therapeutic use, but it may also quell some of the controversy surrounding human cloning, since the embryo is incapable of growing into a human. However, Egli believes he will be able to make cloned stem cells with the normal two sets of chromosomes.

Most human embryonic stem cells used today in research were created from discarded human embryos. The cells are pluripotent, meaning they can differentiate into any type of cell. Cloning has the capacity to create stem cells that are genetically matched to the cell donor; such cells would be ideal for use in cell therapies, because they would not trigger an immune reaction. And they are useful in research, allowing scientists to study cells created from people with specific diseases. 

In 2006, Japanese scientist Shinya Yamanaka developed an alternative method to create genetically matched stem cells called induced pluripotent stem cells, which used chemicals rather than a human egg to turn back the cellular clock in an adult cell. Work with embryonic stem cells—controversial because of the use of embryos—fell out of favor, as most researchers jumped on Yamanaka’s technique.

But there has always been concern that these induced cells were not quite as good as cells derived from embryos. Recent research has suggested that some of the changes—and damage—the adult cell endured during its lifetime would remain when it was turned back into a stem cell, potentially triggering cancer.

Egli, a senior research fellow with the New York Stem Cell Foundation, says his new cells can be compared to induced cells, allowing scientists to spot potential problems in the cells. The research was paid for with private funds from the foundation.

Part of the challenge in carrying out nuclear transfer in humans has been the short supply of eggs. In a companion letter also published online today in Cell Stem Cell, Egli, along with Kevin Eggan and Douglas Melton, two stem cell scientists at Harvard, wrote about the difficulty of getting women to donate their eggs. (The process has the potential for serious side effects and can be painful.)

Instead, in a move that would have been illegal in California and Massachusetts, Egli’s team paid women $8,000 to donate their eggs—the same fee they would receive for donating their eggs to someone battling infertility. The women had already agreed to donate their eggs before they were offered the possibility of contributing to research instead of fertility. Several agreed. Once the scientists learned to leave the egg’s chromosomes intact, the remaining two donations led to one stem cell line each, Egli said.

In 2004, Korean scientist Woo Suk Hwang claimed to produce a stem cell line derived from cloning a human embryo. The work was later discredited. Egli says he was able to succeed where others failed by realizing that there was some key reproductive information in the egg’s genome that was missing in the adult skin cells he used.

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